Two Studies for Patients With High Risk Prostate Cancer Testing Less Intense Treatment for Patients With a Low Gene Risk Score and Testing a More Intense Treatment for Patients With a High Gene Risk Score, The PREDICT-RT Trial

Parallel Phase III Randomized Trials for High Risk Prostate Cancer Evaluating De-Intensification for Lower Genomic Risk and Intensification of Concurrent Therapy for Higher Genomic Risk With Radiation (PREDICT-RT*)

This phase III trial compares less intense hormone therapy and radiation therapy to usual hormone therapy and radiation therapy in treating patients with high risk prostate cancer and low gene risk score. This trial also compares more intense hormone therapy and radiation therapy to usual hormone therapy and radiation therapy in patients with high risk prostate cancer and high gene risk score. Apalutamide may help fight prostate cancer by blocking the use of androgen by the tumor cells. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Giving a shorter hormone therapy treatment may work the same at controlling prostate cancer compared to the usual 24 month hormone therapy treatment in patients with low gene risk score. Adding apalutamide to the usual treatment may increase the length of time without prostate cancer spreading as compared to the usual treatment in patients with high gene risk score.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Adenocarcinoma; Stage III Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Biospecimen Collection; Radiation: Radiation Therapy; Drug: Apalutamide; Procedure: Positron Emission Tomography; Procedure: Computed Tomography; Procedure: Bone Scan; Procedure: Magnetic Resonance Elastography; Drug: Degarelix; Drug: Goserelin; Drug: Histrelin; Drug: Leuprolide; Drug: Relugolix; Drug: Triptorelin; Drug: Bicalutamide; Drug: Buserelin; Drug: Flutamide

Detailed Description

PRIMARY OBJECTIVES:

I. To determine whether men with National Comprehensive Cancer Network (NCCN) high risk prostate cancer who are in the lower 2/3 of Decipher genomic risk (=< 0.85) can be treated with 12 months androgen deprivation therapy (ADT) plus radiation therapy (RT) instead of 24 months ADT+RT and experience non-inferior metastasis-free survival. (De-intensification study) II. To determine whether men with NCCN high risk prostate cancer who are in the upper 1/3 of Decipher genomic risk (> 0.85) or have node-positive disease by conventional imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan) will have a superior metastasis-free survival (MFS) through treatment intensification with apalutamide added to the standard of RT plus 24 month ADT. (Intensification study)

SECONDARY OBJECTIVES:

I. To compare overall survival (OS) between the standard of care (RT plus 24 months of ADT) and either the de-intensification (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) II. To compare time to prostate specific antigen (PSA) failure or start of salvage treatment between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) III. To compare PSA failure-free survival with non-castrate testosterone and no additional therapies between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) IV. To compare MFS judged based on either standard or molecular imaging between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) V. To compare prostate cancer-specific mortality between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) VI. To compare testosterone levels at the time of PSA failure and metastases between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) VII. To compare time to testosterone recovery (defined as a T > 200) between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) VIII. To compare adverse events, both clinician-reported using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 and patient-reported using Patient Reported Outcome (PRO)-CTCAE items, between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies)

EXPLORATORY OBJECTIVES:

I. To compare changes in cardio-metabolic markers, including body mass index, and waist circumference, between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) II. To develop a machine learning/artificial intelligence algorithm for radiotherapy quality assurance. (De-intensification and Intensification studies) III. To perform future translational correlative studies using biological and imaging data. (De-intensification and intensification studies) IV. Impact of position emission tomography (PET) use, measured by the proportion of times each type of imaging was used, in high-risk prostate cancer. (De-intensification and intensification studies)

PATIENT-REPORTED OUTCOMES OBJECTIVES:

PRIMARY OBJECTIVES:

I. To compare sexual and hormonal function related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) II. To compare fatigue, as measured by the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue instrument, between the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study)

SECONDARY OBJECTIVES:

I. To compare depression, as measured by the PROMIS-depression, between the standard of care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) II. To compare depression, as measured by the PROMIS-depression, between the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study)

EXPLORATORY OBJECTIVES:

I. To compare cognition, as measured by the Functional Assessment of Chronic Illness Therapy-Cognitive (FACT-Cog) perceived cognitive abilities subscale, between the standard of care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) II. To compare bowel and urinary function related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) III. To compare fatigue, as measured by the PROMIS-Fatigue instrument, between the standard of care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) IV. To compare sexual and hormonal function related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study) V. To compare bowel and urinary function related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study) VI. To compare cognition, as measured by the Functional Assessment of Chronic Illness Therapy-Cognitive (FACT-Cog) perceived cognitive abilities subscale, between the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study)

OUTLINE: Patients are randomized to 1 of 4 arms.

DE-INTENSIFICATION STUDY (DECIPHER SCORE =< 0.85):

ARM I: Patients undergo radiation therapy (RT) over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin, histrelin, or relugolix and bicalutamide or flutamide) for 24 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin, histrelin, or relugolix and bicalutamide or flutamide) for 12 months in the absence of disease progression or unacceptable toxicity.

INTENSIFICATION STUDY (DECIPHER SCORE > 0.85 OR NODE POSITIVE):

ARM III: Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin, histrelin, or relugolix and bicalutamide or flutamide) for 24 months in the absence of disease progression or unacceptable toxicity.

ARM IV: Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin, histrelin, or relugolix) for 24 months in the absence of disease progression or unacceptable toxicity. Patients also receive apalutamide orally (PO) once daily (QD). Treatment repeats every 90 days for up to 8 cycles (24 months) in the absence of disease progression or unacceptable toxicity.

Patients undergo bone scan, positron emission tomography (PET) scan, computed tomography (CT) scan, and magnetic resonance imaging (MRI) at screening and as clinically indicated and may optionally undergo blood sample collection throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 2753
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Arthur J E Child Comprehensive Cancer Centre
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital and Cancer Center-General Campus
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3H 2R9
      • The Research Institute of the McGill University Health Centre (MUHC)
    • Québec, Quebec, Canada, G1R 2J6
      • CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre
• United States
  • Alaska
    • Fairbanks, Alaska, United States, 99701
      • Fairbanks Memorial Hospital
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Gilbert, Arizona, United States, 85297
      • Arizona Center for Cancer Care - Gilbert
    • Peoria, Arizona, United States, 85381
      • Arizona Center for Cancer Care-Peoria
    • Phoenix, Arizona, United States, 85027
      • Arizona Center for Cancer Care - Phoenix
    • Scottsdale, Arizona, United States, 85258
      • Arizona Center for Cancer Care - Scottsdale
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center-North Campus
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Auburn, California, United States, 95603
      • Sutter Cancer Centers Radiation Oncology Services-Auburn
    • Bakersfield, California, United States, 93301
      • AIS Cancer Center at San Joaquin Community Hospital
    • Berkeley, California, United States, 94704
      • Alta Bates Summit Medical Center-Herrick Campus
    • Cameron Park, California, United States, 95682
      • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    • Chico, California, United States, 95926
      • Enloe Medical Center
    • Corona, California, United States, 92882
      • City of Hope Corona
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Dublin, California, United States, 94568
      • Kaiser Permanente Dublin
    • Encinitas, California, United States, 92024
      • UC San Diego Health System - Encinitas
    • Fremont, California, United States, 94538
      • Kaiser Permanente-Fremont
    • Fremont, California, United States, 94538
      • Washington Hospital
    • Fremont, California, United States, 94538
      • Palo Alto Medical Foundation-Fremont
    • Fresno, California, United States, 93720
      • Kaiser Permanente-Fresno
    • Greenbrae, California, United States, 94904
      • Marin General Hospital
    • Irvine, California, United States, 92618
      • City of Hope at Irvine Lennar
    • Irvine, California, United States, 92612
      • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Lancaster, California, United States, 93534
      • City of Hope Antelope Valley
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Los Angeles, California, United States, 90033
      • Los Angeles General Medical Center
    • Marysville, California, United States, 95901
      • Fremont - Rideout Cancer Center
    • Modesto, California, United States, 95355
      • Memorial Medical Center
    • Modesto, California, United States, 95356
      • Kaiser Permanente-Modesto
    • Napa, California, United States, 94558
      • Providence Queen of The Valley
    • Oakland, California, United States, 94611
      • Kaiser Permanente-Oakland
    • Orange, California, United States, 92868
      • UC Irvine Health/Chao Family Comprehensive Cancer Center
    • Orange, California, United States, 92868
      • Saint Joseph Hospital - Orange
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute Palo Alto
    • Palo Alto, California, United States, 94301
      • Palo Alto Medical Foundation Health Care
    • Roseville, California, United States, 95661
      • Kaiser Permanente-Roseville
    • Roseville, California, United States, 95661
      • Sutter Cancer Centers Radiation Oncology Services-Roseville
    • Sacramento, California, United States, 95816
      • Sutter Medical Center Sacramento
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • Sacramento, California, United States, 95814
      • Kaiser Permanente Downtown Commons
    • Sacramento, California, United States, 95823
      • Kaiser Permanente-South Sacramento
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital
    • San Diego, California, United States, 92121
      • California Protons Cancer Therapy Center
    • San Francisco, California, United States, 94115
      • Kaiser Permanente-San Francisco
    • San Francisco, California, United States, 94158
      • UCSF Medical Center-Mission Bay
    • San Jose, California, United States, 95119
      • Kaiser Permanente-Santa Teresa-San Jose
    • San Jose, California, United States, 95124
      • Stanford Cancer Center South Bay
    • San Leandro, California, United States, 94577
      • Kaiser Permanente San Leandro
    • San Mateo, California, United States, 94402
      • UCSF Cancer Center - San Mateo
    • Santa Barbara, California, United States, 93105
      • Ridley-Tree Cancer Center
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Medical Center - Santa Clara
    • Santa Rosa, California, United States, 95403
      • Kaiser Permanente-Santa Rosa
    • South Pasadena, California, United States, 91030
      • City of Hope South Pasadena
    • South San Francisco, California, United States, 94080
      • Kaiser Permanente-South San Francisco
    • Sunnyvale, California, United States, 94086
      • Palo Alto Medical Foundation-Sunnyvale
    • Tarzana, California, United States, 91356
      • Cedars-Sinai Cancer - Tarzana
    • Torrance, California, United States, 90509
      • Torrance Memorial Medical Center
    • Torrance, California, United States, 90505
      • Torrance Memorial Physician Network - Cancer Care
    • Torrance, California, United States, 90503
      • City of Hope South Bay
    • Truckee, California, United States, 96161
      • Gene Upshaw Memorial Tahoe Forest Cancer Center
    • Upland, California, United States, 91786
      • City of Hope Upland
    • Vallejo, California, United States, 94589
      • Kaiser Permanente-Vallejo
    • Walnut Creek, California, United States, 94596
      • Kaiser Permanente-Walnut Creek
    • Walnut Creek, California, United States, 94598
      • John Muir Medical Center-Walnut Creek
    • Walnut Creek, California, United States, 94598
      • BASS Medical Group - Lennon
  • Colorado
    • Aurora, Colorado, United States, 80045
      • UCHealth University of Colorado Hospital
    • Boulder, Colorado, United States, 80304
      • Rocky Mountain Cancer Centers-Boulder
    • Colorado Springs, Colorado, United States, 80909
      • UCHealth Memorial Hospital Central
    • Colorado Springs, Colorado, United States, 80920
      • Memorial Hospital North
    • Edwards, Colorado, United States, 81632
      • Shaw Cancer Center
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
    • Fort Collins, Colorado, United States, 80528
      • Cancer Care and Hematology-Fort Collins
    • Grand Junction, Colorado, United States, 81501
      • Saint Mary's Hospital and Regional Medical Center
    • Greeley, Colorado, United States, 80631
      • UCHealth Greeley Hospital
    • Greeley, Colorado, United States, 80631
      • Banner North Colorado Medical Center
    • Highlands Ranch, Colorado, United States, 80129
      • UCHealth Highlands Ranch Hospital
    • Loveland, Colorado, United States, 80538
      • Medical Center of the Rockies
    • Loveland, Colorado, United States, 80539
      • Banner North Colorado Medical Center - Loveland Campus
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • Hartford HealthCare - Saint Vincent's Medical Center
    • Derby, Connecticut, United States, 06418
      • Smilow Cancer Hospital-Derby Care Center
    • Fairfield, Connecticut, United States, 06824
      • Smilow Cancer Hospital Care Center-Fairfield
    • Greenwich, Connecticut, United States, 06830
      • Smilow Cancer Hospital Care Center at Greenwich
    • Guilford, Connecticut, United States, 06437
      • Smilow Cancer Hospital Care Center - Guilford
    • Hartford, Connecticut, United States, 06105
      • Smilow Cancer Hospital Care Center at Saint Francis
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • Meriden, Connecticut, United States, 06451
      • Midstate Medical Center
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
    • North Haven, Connecticut, United States, 06473
      • Yale-New Haven Hospital North Haven Medical Center
    • Orange, Connecticut, United States, 06477
      • Smilow Cancer Hospital-Orange Care Center
    • Stamford, Connecticut, United States, 06904
      • Stamford Hospital/Bennett Cancer Center
    • Stamford, Connecticut, United States, 06902
      • Smilow Cancer Hospital Care Center at Long Ridge
    • Trumbull, Connecticut, United States, 06611
      • Smilow Cancer Hospital Care Center-Trumbull
    • Waterford, Connecticut, United States, 06385
      • Smilow Cancer Hospital Care Center - Waterford
  • Delaware
    • Dover, Delaware, United States, 19901
      • Bayhealth Hospital Kent Campus
    • Newark, Delaware, United States, 19713
      • Helen F Graham Cancer Center
    • Newark, Delaware, United States, 19713
      • Medical Oncology Hematology Consultants PA
  • Florida
    • Aventura, Florida, United States, 33180
      • Mount Sinai Comprehensive Cancer Center at Aventura
    • Bay Pines, Florida, United States, 33744
      • Bay Pines VA Healthcare System
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital
    • Gainesville, Florida, United States, 32610
      • UF Health Cancer Institute - Gainesville
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
    • Lakewood Rch, Florida, United States, 34202
      • GenesisCare USA - Lakewood Ranch
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
    • Plantation, Florida, United States, 33324
      • GenesisCare USA - Plantation
    • Plantation, Florida, United States, 33324
      • Miami Cancer Institute at Plantation
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
    • Atlanta, Georgia, United States, 30342
      • Emory Saint Joseph's Hospital
    • Atlanta, Georgia, United States, 30303
      • Grady Health System
    • Atlanta, Georgia, United States, 30308
      • Emory Proton Therapy Center
    • Decatur, Georgia, United States, 30033
      • Emory Decatur Hospital
    • Johns Creek, Georgia, United States, 30097
      • Emory Johns Creek Hospital
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96817
      • The Cancer Center of Hawaii-Liliha
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Cancer Care Inc - Waterfront Plaza
    • Honolulu, Hawaii, United States, 96813
      • Queen's Cancer Cenrer - POB I
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
    • Honolulu, Hawaii, United States, 96817
      • Queen's Cancer Center - Kuakini
    • ‘Aiea, Hawaii, United States, 96701
      • Hawaii Cancer Care - Westridge
    • ‘Aiea, Hawaii, United States, 96701
      • Pali Momi Medical Center
    • ‘Aiea, Hawaii, United States, 96701
      • The Cancer Center of Hawaii-Pali Momi
    • ‘Ewa Beach, Hawaii, United States, 96706
      • The Queen's Medical Center - West Oahu
  • Illinois
    • Alton, Illinois, United States, 62002
      • Alton Memorial Hospital
    • Aurora, Illinois, United States, 60504
      • Rush-Copley Medical Center
    • Barrington, Illinois, United States, 60010
      • Advocate Good Shepherd Hospital
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Chicago, Illinois, United States, 60657
      • Advocate Illinois Masonic Medical Center
    • Chicago, Illinois, United States, 60612
      • Rush MD Anderson Cancer Center
    • Crystal Lake, Illinois, United States, 60014
      • AMG Crystal Lake - Oncology
    • Danville, Illinois, United States, 61832
      • Carle at The Riverfront
    • DeKalb, Illinois, United States, 60115
      • Northwestern Medicine Cancer Center Kishwaukee
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Downers Grove, Illinois, United States, 60515
      • Advocate Good Samaritan Hospital
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Elgin, Illinois, United States, 60123
      • Advocate Sherman Hospital
    • Elmhurst, Illinois, United States, 60126
      • Elmhurst Memorial Hospital
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Geneva, Illinois, United States, 60134
      • Northwestern Medicine Cancer Center Delnor
    • Glenview, Illinois, United States, 60026
      • Northwestern Medicine Glenview Outpatient Center
    • Grayslake, Illinois, United States, 60030
      • Northwestern Medicine Grayslake Outpatient Center
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital
    • Hazel Crest, Illinois, United States, 60429
      • Advocate South Suburban Hospital
    • Hines, Illinois, United States, 60141
      • Edward Hines Jr VA Hospital
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • Lake Forest, Illinois, United States, 60045
      • Northwestern Medicine Lake Forest Hospital
    • Libertyville, Illinois, United States, 60048
      • Condell Memorial Hospital
    • Libertyville, Illinois, United States, 60048
      • AMG Libertyville - Oncology
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Mattoon, Illinois, United States, 61938
      • Carle Physician Group-Mattoon/Charleston
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Naperville, Illinois, United States, 60540
      • Edward Hospital/Cancer Center
    • New Lenox, Illinois, United States, 60451
      • UC Comprehensive Cancer Center at Silver Cross
    • O'Fallon, Illinois, United States, 62269
      • HSHS Saint Elizabeth's Hospital
    • Oak Brook, Illinois, United States, 60523
      • Northwestern Medicine Oak Brook
    • Oak Lawn, Illinois, United States, 60453-2699
      • Advocate Christ Medical Center
    • Orland Park, Illinois, United States, 60462
      • University of Chicago Medicine-Orland Park
    • Orland Park, Illinois, United States, 60462
      • Northwestern Medicine Orland Park
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Palos Heights, Illinois, United States, 60463
      • Advocate High Tech Medical Park
    • Park Ridge, Illinois, United States, 60068
      • Advocate Lutheran General Hospital
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Plainfield, Illinois, United States, 60585
      • Edward Hospital/Cancer Center?Plainfield
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare-Princeton
    • Rockford, Illinois, United States, 61114
      • UW Health Carbone Cancer Center Rockford
    • Shiloh, Illinois, United States, 62269
      • Memorial Hospital East
    • Springfield, Illinois, United States, 62781
      • Springfield Memorial Hospital
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Warrenville, Illinois, United States, 60555
      • Northwestern Medicine Cancer Center Warrenville
    • Washington, Illinois, United States, 61571
      • Illinois CancerCare - Washington
  • Indiana
    • Avon, Indiana, United States, 46123
      • IU Health West Hospital
    • Carmel, Indiana, United States, 46032
      • IU Health North Hospital
    • Crown Point, Indiana, United States, 46307
      • UChicago Medicine Northwest Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • IU Health Methodist Hospital
  • Iowa
    • Ankeny, Iowa, United States, 50023
      • UI Health Care Mission Cancer and Blood - Ankeny Clinic
    • Cedar Rapids, Iowa, United States, 52403
      • Mercy Hospital
    • Cedar Rapids, Iowa, United States, 52403
      • Oncology Associates at Mercy Medical Center
    • Cedar Rapids, Iowa, United States, 52402
      • Saint Luke's Hospital
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Broadlawns Medical Center
    • Des Moines, Iowa, United States, 50309
      • UI Health Care Mission Cancer and Blood - Des Moines Clinic
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Olathe, Kansas, United States, 66061
      • The University of Kansas Cancer Center - Olathe
    • Overland Park, Kansas, United States, 66210
      • University of Kansas Cancer Center-Overland Park
    • Salina, Kansas, United States, 67401
      • Salina Regional Health Center
    • Topeka, Kansas, United States, 66606
      • University of Kansas Health System Saint Francis Campus
    • Westwood, Kansas, United States, 66205
      • University of Kansas Hospital-Westwood Cancer Center
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Hospitals Wichita
    • Wichita, Kansas, United States, 67214
      • Wesley Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Saint Joseph Hospital East
    • Louisville, Kentucky, United States, 40202
      • The James Graham Brown Cancer Center at University of Louisville
    • Louisville, Kentucky, United States, 40245
      • UofL Health Medical Center Northeast
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center
    • Metairie, Louisiana, United States, 70006
      • East Jefferson General Hospital
    • Metairie, Louisiana, United States, 70006
      • LSU Healthcare Network / Metairie Multi-Specialty Clinic
    • Metairie, Louisiana, United States, 70002
      • Mary Bird Perkins Cancer Center - Metairie
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
  • Maine
    • Bath, Maine, United States, 04530
      • MaineHealth Coastal Cancer Treatment Center
    • Portland, Maine, United States, 04102
      • MaineHealth Maine Medical Center - Portland
    • Rockport, Maine, United States, 04856
      • Penobscot Bay Medical Center
    • Sanford, Maine, United States, 04073
      • MaineHealth Cancer Care Center of York County
    • Scarborough, Maine, United States, 04074
      • MaineHealth Maine Medical Center- Scarborough
    • South Portland, Maine, United States, 04106
      • MaineHealth Cancer Care and IV Therapy - South Portland
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Luminis Health Anne Arundel Medical Center
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Baltimore, Maryland, United States, 21201
      • Veterans Administration Medical Center-Baltimore
    • Baltimore, Maryland, United States, 21201
      • Maryland Proton Treatment Center
    • Bel Air, Maryland, United States, 21014
      • UM Upper Chesapeake Medical Center
    • Bethesda, Maryland, United States, 20814
      • Suburban Hospital
    • Easton, Maryland, United States, 21601
      • University of Maryland Shore Medical Center at Easton
    • Glen Burnie, Maryland, United States, 21061
      • UM Baltimore Washington Medical Center/Tate Cancer Center
    • Largo, Maryland, United States, 20774
      • UM Capital Region Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Hyannis, Massachusetts, United States, 02601
      • Cape Cod Hospital
    • Milford, Massachusetts, United States, 01757
      • Dana-Farber/Brigham and Women's Cancer Center at Milford Regional
    • South Weymouth, Massachusetts, United States, 02190
      • Dana-Farber/Brigham and Women's Cancer Center at South Shore
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Rogel Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
    • Bay City, Michigan, United States, 48706
      • McLaren Cancer Institute-Bay City
    • Brighton, Michigan, United States, 48114
      • Trinity Health IHA Medical Group Hematology Oncology - Brighton
    • Brighton, Michigan, United States, 48116
      • University of Michigan - Brighton Center for Specialty Care
    • Brighton, Michigan, United States, 48114
      • Trinity Health Medical Center - Brighton
    • Brownstown, Michigan, United States, 48183
      • Henry Ford Cancer Institute-Downriver
    • Canton, Michigan, United States, 48188
      • Trinity Health IHA Medical Group Hematology Oncology - Canton
    • Canton, Michigan, United States, 48188
      • Trinity Health Medical Center - Canton
    • Chelsea, Michigan, United States, 48118
      • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
    • Chelsea, Michigan, United States, 48118
      • Chelsea Hospital
    • Clarkston, Michigan, United States, 48346
      • McLaren Cancer Institute-Clarkston
    • Clarkston, Michigan, United States, 48346
      • Michigan Healthcare Professionals Clarkston
    • Clinton Township, Michigan, United States, 48038
      • Henry Ford Macomb Hospital-Clinton Township
    • Dearborn, Michigan, United States, 48126
      • Henry Ford Medical Center-Fairlane
    • Dearborn, Michigan, United States, 48124
      • Corewell Health Dearborn Hospital
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Farmington Hills, Michigan, United States, 48334
      • Weisberg Cancer Treatment Center
    • Farmington Hills, Michigan, United States, 48334
      • Michigan Healthcare Professionals Farmington
    • Flint, Michigan, United States, 48532
      • McLaren Cancer Institute-Flint
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Trinity Health Grand Rapids Hospital
    • Grand Rapids, Michigan, United States, 49503
      • Corewell Health Grand Rapids Hospitals - Butterworth Hospital
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Lansing, Michigan, United States, 48910
      • Karmanos Cancer Institute at McLaren Greater Lansing
    • Lansing, Michigan, United States, 48912
      • University of Michigan Health - Sparrow Lansing
    • Lapeer, Michigan, United States, 48446
      • McLaren Cancer Institute-Lapeer Region
    • Livonia, Michigan, United States, 48154
      • Trinity Health Saint Mary Mercy Livonia Hospital
    • Macomb, Michigan, United States, 48044
      • Michigan Healthcare Professionals Macomb
    • Madison Heights, Michigan, United States, 48071
      • Michigan Healthcare Professionals Madison Heights
    • Mount Clemens, Michigan, United States, 48043
      • McLaren Cancer Institute-Macomb
    • Mount Pleasant, Michigan, United States, 48858
      • McLaren Cancer Institute-Central Michigan
    • Niles, Michigan, United States, 49120
      • Corewell Health Lakeland Hospitals - Niles Hospital
    • Novi, Michigan, United States, 48377
      • Henry Ford Medical Center-Columbus
    • Port Huron, Michigan, United States, 48060
      • McLaren-Port Huron
    • Royal Oak, Michigan, United States, 48073
      • Corewell Health William Beaumont University Hospital
    • Saginaw, Michigan, United States, 48601
      • MyMichigan Medical Center Saginaw
    • Saint Joseph, Michigan, United States, 49085
      • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
    • Saint Joseph, Michigan, United States, 49085
      • Corewell Health Lakeland Hospitals - Saint Joseph Hospital
    • Shelby, Michigan, United States, 48315
      • Henry Ford Macomb Health Center - Shelby Township
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Troy, Michigan, United States, 48098
      • Michigan Healthcare Professionals Troy
    • Troy, Michigan, United States, 48085
      • Corewell Health Beaumont Troy Hospital
    • West Bloomfield, Michigan, United States, 48322
      • Henry Ford West Bloomfield Hospital
    • Wyoming, Michigan, United States, 49519
      • University of Michigan Health - West
    • Ypsilanti, Michigan, United States, 48197
      • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
  • Minnesota
    • Albert Lea, Minnesota, United States, 56007
      • Mayo Clinic Health System in Albert Lea
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Duluth, Minnesota, United States, 55805
      • Miller-Dwan Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Monticello, Minnesota, United States, 55362
      • Monticello Cancer Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • City of Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center at Saint Peters Hospital
    • Columbia, Missouri, United States, 65212
      • MU Health - University Hospital/Ellis Fischel Cancer Center
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center at West County Hospital
    • Farmington, Missouri, United States, 63640
      • Parkland Health Center - Farmington
    • Joplin, Missouri, United States, 64804
      • Freeman Health System
    • Kansas City, Missouri, United States, 64154
      • University of Kansas Cancer Center - North
    • Lee's Summit, Missouri, United States, 64064
      • University of Kansas Cancer Center - Lee's Summit
    • North Kansas City, Missouri, United States, 64116
      • University of Kansas Cancer Center at North Kansas City Hospital
    • Rolla, Missouri, United States, 65401
      • Phelps Health Delbert Day Cancer Institute
    • Sainte Genevieve, Missouri, United States, 63670
      • Sainte Genevieve County Memorial Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • St Louis, Missouri, United States, 63129
      • Siteman Cancer Center-South County
    • St Louis, Missouri, United States, 63136
      • Siteman Cancer Center at Christian Hospital
    • St Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • St Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Sullivan, Missouri, United States, 63080
      • Missouri Baptist Sullivan Hospital
    • Sunset Hills, Missouri, United States, 63127
      • BJC Outpatient Center at Sunset Hills
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Great Falls, Montana, United States, 59405
      • Benefis Sletten Cancer Institute
  • Nebraska
    • Bellevue, Nebraska, United States, 68123
      • Nebraska Medicine-Bellevue
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
    • Omaha, Nebraska, United States, 68118
      • Nebraska Medicine-Village Pointe
  • New Hampshire
    • Concord, New Hampshire, United States, 03301
      • New Hampshire Oncology Hematology PA-Concord
    • Exeter, New Hampshire, United States, 03833
      • Exeter Hospital
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
    • Manchester, New Hampshire, United States, 03103
      • Solinsky Center for Cancer Care
  • New Jersey
    • Belleville, New Jersey, United States, 07109
      • Clara Maass Medical Center
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • Egg Harbor, New Jersey, United States, 08234
      • AtlantiCare Surgery Center
    • Elizabeth, New Jersey, United States, 07207
      • Trinitas Hospital and Comprehensive Cancer Center - Williamson Street Campus
    • Englewood, New Jersey, United States, 07631
      • Englewood Hospital and Medical Center
    • Hamilton, New Jersey, United States, 08690
      • The Cancer Institute of New Jersey Hamilton
    • Jersey City, New Jersey, United States, 07302
      • Jersey City Medical Center
    • Livingston, New Jersey, United States, 07039
      • Saint Barnabas Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
    • Newark, New Jersey, United States, 07101
      • Rutgers New Jersey Medical School
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
    • Paramus, New Jersey, United States, 07652
      • The Valley Hospital - Luckow Pavilion
    • Ridgewood, New Jersey, United States, 07450
      • Valley Health System Ridgewood Campus
    • Sewell, New Jersey, United States, 08080
      • Sidney Kimmel Cancer Center Washington Township
    • Somerville, New Jersey, United States, 08876
      • Robert Wood Johnson University Hospital Somerset
    • Toms River, New Jersey, United States, 08755
      • Community Medical Center
    • Voorhees Township, New Jersey, United States, 08043
      • MD Anderson Cancer Center at Cooper-Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Lovelace Medical Center-Saint Joseph Square
    • Albuquerque, New Mexico, United States, 87109
      • Lovelace Radiation Oncology
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Cancer Center
    • Albuquerque, New Mexico, United States, 87110
      • Presbyterian Kaseman Hospital
    • Rio Rancho, New Mexico, United States, 87124
      • Presbyterian Rust Medical Center/Jorgensen Cancer Center
  • New York
    • Bay Shore, New York, United States, 11706
      • Northwell Health Imbert Cancer Center
    • Brooklyn, New York, United States, 11215
      • New York-Presbyterian/Brooklyn Methodist Hospital
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Canandiaqua, New York, United States, 14424
      • Sands Cancer Center
    • Cooperstown, New York, United States, 13326
      • Mary Imogene Bassett Hospital
    • Dansville, New York, United States, 14437
      • Noyes Memorial Hospital/Myers Cancer Center
    • Flushing, New York, United States, 11355
      • The New York Hospital Medical Center of Queens
    • Forest Hills, New York, United States, 11375
      • Northwell Health Physicians Partners Radiation Medicine at Queens
    • Glens Falls, New York, United States, 12801
      • Glens Falls Hospital
    • Greenlawn, New York, United States, 11740
      • Northwell Health Cancer Institute at Huntington
    • Lake Success, New York, United States, 11042
      • Northwell Health/Center for Advanced Medicine
    • New York, New York, United States, 10032
      • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
    • New York, New York, United States, 10065
      • NYP/Weill Cornell Medical Center
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center at NYU Langone
    • New York, New York, United States, 10075
      • Lenox Hill Hospital
    • New York, New York, United States, 10065
      • Manhattan Eye Ear and Throat Hospital
    • Rego Park, New York, United States, 11374
      • Queens Cancer Center
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Rochester, New York, United States, 14620
      • Highland Hospital
    • Sleepy Hollow, New York, United States, 10591
      • Phelps Memorial Hospital Center
    • Staten Island, New York, United States, 10305
      • Staten Island University Hospital
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center-Einstein Campus
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center - Moses Campus
    • Valhalla, New York, United States, 10595
      • Westchester Medical Center
    • Webster, New York, United States, 14580
      • Wilmot Cancer Institute at Webster
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Duke Cancer Center Cary
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center/Levine Cancer Institute
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center
    • Charlotte, North Carolina, United States, 28210
      • Atrium Health Pineville/LCI-Pineville
    • Charlotte, North Carolina, United States, 28262
      • Atrium Health University City/LCI-University
    • Charlotte, North Carolina, United States, 28277
      • Levine Cancer Institute-Ballantyne
    • Concord, North Carolina, United States, 28025
      • Atrium Health Cabarrus/LCI-Concord
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Durham, North Carolina, United States, 27705
      • Durham VA Medical Center
    • Huntersville, North Carolina, United States, 28078
      • Novant Health Cancer Institute - Huntersville
    • Huntersville, North Carolina, United States, 28078
      • Novant Health Presbyterian Medical Center Huntersville
    • Matthews, North Carolina, United States, 28105
      • Matthews Radiation Oncology Center
    • Matthews, North Carolina, United States, 28105
      • Novant Health Cancer Institute - Matthews
    • Monroe, North Carolina, United States, 28112
      • Atrium Health Union/LCI-Union
    • Mooresville, North Carolina, United States, 28117
      • Novant Health Cancer Institute - Mooresville
    • Raleigh, North Carolina, United States, 27609
      • Duke Cancer Center Raleigh
    • Raleigh, North Carolina, United States, 27607
      • UNC Health Cancer Care Raleigh
    • Raleigh, North Carolina, United States, 27614
      • UNC Health Cancer Care Wakefield
    • Supply, North Carolina, United States, 28462
      • Novant Cancer Institute Radiation Oncology - Supply
    • Wilmington, North Carolina, United States, 28401
      • Novant Health New Hanover Regional Medical Center
    • Wilmington, North Carolina, United States, 28401
      • Novant Health Cancer Institute Radiation Oncology - Wilmington
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
    • Winston-Salem, North Carolina, United States, 27103
      • Novant Health Forsyth Medical Center
  • North Dakota
    • Grand Forks, North Dakota, United States, 58201
      • Altru Cancer Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • Cleveland Clinic Akron General
    • Akron, Ohio, United States, 44304
      • Summa Health System - Akron Campus
    • Barberton, Ohio, United States, 44203
      • Summa Health System - Barberton Campus
    • Canton, Ohio, United States, 44710
      • Aultman Health Foundation
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center
    • Delaware, Ohio, United States, 43015
      • Delaware Health Center-Grady Cancer Center
    • Dublin, Ohio, United States, 43016
      • Dublin Methodist Hospital
    • Mansfield, Ohio, United States, 44903
      • OhioHealth Mansfield Hospital
    • Marion, Ohio, United States, 43302
      • OhioHealth Marion General Hospital
    • Medina, Ohio, United States, 44256
      • Summa Health Medina Medical Center
    • Sylvania, Ohio, United States, 43560
      • ProMedica Flower Hospital
  • Oklahoma
    • Lawton, Oklahoma, United States, 73505
      • Cancer Centers of Southwest Oklahoma Research
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Bend, Oregon, United States, 97701
      • Saint Charles Health System
    • Gresham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
    • Oregon City, Oregon, United States, 97045
      • Providence Willamette Falls Medical Center
    • Portland, Oregon, United States, 97210
      • Legacy Good Samaritan Hospital and Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
    • Tualatin, Oregon, United States, 97062
      • Legacy Meridian Park Hospital
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Saint Luke's Cancer Center - Allentown
    • Altoona, Pennsylvania, United States, 16601
      • UPMC Altoona
    • Beaver, Pennsylvania, United States, 15009
      • UPMC-Heritage Valley Health System Beaver
    • Bethlehem, Pennsylvania, United States, 18015
      • Saint Luke's University Hospital-Bethlehem Campus
    • Broomall, Pennsylvania, United States, 19008
      • Crozer-Keystone Regional Cancer Center at Broomall
    • Carlisle, Pennsylvania, United States, 17015
      • Carlisle Regional Cancer Center
    • Chadds Ford, Pennsylvania, United States, 19317
      • Christiana Care Health System-Concord Health Center
    • Chambersburg, Pennsylvania, United States, 17201
      • Chambersburg Hospital
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Drexel Hill, Pennsylvania, United States, 19026
      • Delaware County Memorial Hospital
    • Easton, Pennsylvania, United States, 18045
      • Saint Luke's Hospital-Anderson Campus
    • Ephrata, Pennsylvania, United States, 17522
      • Ephrata Cancer Center
    • Erie, Pennsylvania, United States, 16505
      • UPMC Hillman Cancer Center Erie
    • Erie, Pennsylvania, United States, 16544
      • Saint Vincent Hospital
    • Farrell, Pennsylvania, United States, 16121
      • UPMC Cancer Center at UPMC Horizon
    • Gettysburg, Pennsylvania, United States, 17325
      • Adams Cancer Center
    • Glen Mills, Pennsylvania, United States, 19342
      • Crozer Regional Cancer Center at Brinton Lake
    • Greensburg, Pennsylvania, United States, 15601
      • UPMC Cancer Centers - Arnold Palmer Pavilion
    • Harrisburg, Pennsylvania, United States, 17109
      • UPMC Pinnacle Cancer Center/Community Osteopathic Campus
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Milton S Hershey Medical Center
    • Indiana, Pennsylvania, United States, 15701
      • IRMC Cancer Center
    • Jefferson Hills, Pennsylvania, United States, 15025
      • Jefferson Hospital
    • Johnstown, Pennsylvania, United States, 15901
      • UPMC-Johnstown/John P. Murtha Regional Cancer Center
    • Lebanon, Pennsylvania, United States, 17042
      • Sechler Family Cancer Center
    • Lewisburg, Pennsylvania, United States, 17837
      • Geisinger Medical Oncology-Lewisburg
    • McKeesport, Pennsylvania, United States, 15132
      • UPMC Cancer Center at UPMC McKeesport
    • Meadville, Pennsylvania, United States, 16335
      • Yolanda G Barco Oncology Institute
    • Mechanicsburg, Pennsylvania, United States, 17050
      • UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion
    • Monroeville, Pennsylvania, United States, 15146
      • Forbes Hospital
    • Monroeville, Pennsylvania, United States, 15146
      • UPMC Cancer Center - Monroeville
    • Moon Township, Pennsylvania, United States, 15108
      • UPMC Hillman Cancer Center in Coraopolis
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Philadelphia, Pennsylvania, United States, 19141
      • Einstein Medical Center Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15224
      • West Penn Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC-Magee Womens Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute (UPCI)
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC-Shadyside Hospital
    • Pittsburgh, Pennsylvania, United States, 15215
      • UPMC-Saint Margaret
    • Pittsburgh, Pennsylvania, United States, 15237
      • UPMC-Passavant Hospital
    • Pittsburgh, Pennsylvania, United States, 15243
      • UPMC-Saint Clair Hospital Cancer Center
    • Pottsville, Pennsylvania, United States, 17901
      • Geisinger Cancer Services-Pottsville
    • Quakertown, Pennsylvania, United States, 18951
      • Saint Luke's Hospital-Quakertown Campus
    • Quakertown, Pennsylvania, United States, 18951
      • Saint Luke's Hospital - Upper Bucks Campus
    • Seneca, Pennsylvania, United States, 16346
      • UPMC Cancer Center at UPMC Northwest
    • Stroudsburg, Pennsylvania, United States, 18360
      • Saint Luke's Hospital - Monroe Campus
    • Uniontown, Pennsylvania, United States, 15401
      • UPMC Uniontown Hospital Radiation Oncology
    • Uniontown, Pennsylvania, United States, 15401
      • UPMC Cancer Center-Uniontown
    • Washington, Pennsylvania, United States, 15301
      • UPMC Washington Hospital Radiation Oncology
    • Washington, Pennsylvania, United States, 15301
      • UPMC Cancer Center-Washington
    • West Chester, Pennsylvania, United States, 19380
      • Chester County Hospital
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
    • Wexford, Pennsylvania, United States, 15090
      • Wexford Health and Wellness Pavilion
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley/Henry Cancer Center
    • Williamsport, Pennsylvania, United States, 17754
      • Divine Providence Hospital
    • Willow Grove, Pennsylvania, United States, 19090
      • Asplundh Cancer Pavilion
    • York, Pennsylvania, United States, 17403
      • WellSpan Health-York Cancer Center
    • York, Pennsylvania, United States, 17408
      • UPMC Memorial
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
    • Westerly, Rhode Island, United States, 02891
      • Smilow Cancer Hospital Care Center - Westerly
  • South Carolina
    • Bluffton, South Carolina, United States, 29910
      • Saint Joseph's/Candler - Bluffton Campus
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Florence, South Carolina, United States, 29505
      • MUSC Health Florence Medical Center
    • Greenville, South Carolina, United States, 29607
      • Saint Francis Cancer Center
    • Greenville, South Carolina, United States, 29601
      • Saint Francis Hospital
    • Greenwood, South Carolina, United States, 29646
      • Self Regional Healthcare
    • Greer, South Carolina, United States, 29651
      • Gibbs Cancer Center-Pelham
    • Hilton Head Island, South Carolina, United States, 29926
      • The Radiation Oncology Center-Hilton Head/Bluffton
    • Myrtle Beach, South Carolina, United States, 29577
      • Carolina Regional Cancer Center
    • Okatie, South Carolina, United States, 29909
      • Beaufort Memorial/New River Cancer Center
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • Covenant Health Cancer Centers
    • Maryville, Tennessee, United States, 37804
      • Covenant Health Oncology Group - Maryville
    • Oak Ridge, Tennessee, United States, 37830
      • Covenant Health Oncology Group - Oak Ridge
  • Texas
    • Baytown, Texas, United States, 77521
      • Houston Methodist San Jacinto Hospital
    • Conroe, Texas, United States, 77384
      • MD Anderson in The Woodlands
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77070
      • Methodist Willowbrook Hospital
    • Houston, Texas, United States, 77094
      • Houston Methodist West Hospital
    • Houston, Texas, United States, 77079
      • MD Anderson West Houston
    • League City, Texas, United States, 77573
      • MD Anderson League City
    • McKinney, Texas, United States, 75071
      • Texas Oncology-McKinney
    • Nassau Bay, Texas, United States, 77058
      • Houston Methodist Saint John Hospital
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
    • Sugar Land, Texas, United States, 77478
      • MD Anderson in Sugar Land
    • Sugar Land, Texas, United States, 77479
      • Houston Methodist Sugar Land Hospital
    • The Woodlands, Texas, United States, 77385
      • Houston Methodist The Woodlands Hospital
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital / Huntsman Intermountain Cancer Center
    • Farmington, Utah, United States, 84025
      • Farmington Health Center
    • Logan, Utah, United States, 84321
      • Logan Regional Hospital
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center
    • Riverton, Utah, United States, 84065
      • Riverton Hospital
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists-Salt Lake City
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
    • Salt Lake City, Utah, United States, 84106
      • University of Utah Sugarhouse Health Center
    • St. George, Utah, United States, 84770
      • Saint George Regional Medical Center
  • Vermont
    • Berlin Corners, Vermont, United States, 05602
      • Central Vermont Medical Center/National Life Cancer Treatment
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
    • Saint Johnsbury, Vermont, United States, 05819
      • Dartmouth Cancer Center - North
  • Virginia
    • Alexandria, Virginia, United States, 22304
      • Inova Alexandria Hospital
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute
    • Fairfax, Virginia, United States, 22033
      • Inova Fair Oaks Hospital
    • Midlothian, Virginia, United States, 23114
      • Bon Secours Saint Francis Medical Center
    • Richmond, Virginia, United States, 23230
      • Bon Secours Cancer Institute at Reynolds Crossing
    • Richmond, Virginia, United States, 23298
      • VCU Massey Comprehensive Cancer Center
    • Roanoke, Virginia, United States, 24014
      • Oncology and Hematology Associates of Southwest Virginia
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Vancouver, Washington, United States, 98686
      • Legacy Salmon Creek Hospital
    • Vancouver, Washington, United States, 98684
      • Legacy Cancer Institute Medical Oncology and Day Treatment
    • Walla Walla, Washington, United States, 99362
      • Providence Saint Mary Regional Cancer Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Healthcare
    • Wheeling, West Virginia, United States, 26003
      • Wheeling Hospital/Schiffler Cancer Center
  • Wisconsin
    • Antigo, Wisconsin, United States, 54409
      • Langlade Hospital and Cancer Center
    • Appleton, Wisconsin, United States, 54911
      • ThedaCare Regional Cancer Center
    • Appleton, Wisconsin, United States, 54915
      • Ascension Saint Elizabeth Hospital
    • Ashland, Wisconsin, United States, 54806
      • Northwest Wisconsin Cancer Center
    • Brookfield, Wisconsin, United States, 53045
      • Ascension Southeast Wisconsin Hospital - Elmbrook Campus
    • Burlington, Wisconsin, United States, 53105
      • Aurora Cancer Care-Southern Lakes VLCC
    • Chilton, Wisconsin, United States, 53014
      • Ascension Calumet Hospital
    • Eau Claire, Wisconsin, United States, 54701
      • Marshfield Medical Center-EC Cancer Center
    • Eau Claire, Wisconsin, United States, 54701
      • HSHS Sacred Heart Hospital
    • Franklin, Wisconsin, United States, 53132
      • Ascension Saint Francis - Reiman Cancer Center
    • Germantown, Wisconsin, United States, 53022
      • Aurora Health Care Germantown Health Center
    • Grafton, Wisconsin, United States, 53024
      • Aurora Cancer Care-Grafton
    • Green Bay, Wisconsin, United States, 54311
      • Aurora BayCare Medical Center
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital Cancer Center Green Bay
    • Green Bay, Wisconsin, United States, 54303
      • Saint Vincent Hospital Cancer Center at Saint Mary's
    • Johnson Creek, Wisconsin, United States, 53038
      • University of Wisconsin Carbone Cancer Center - Johnson Creek
    • Kenosha, Wisconsin, United States, 53142
      • Aurora Cancer Care-Kenosha South
    • La Crosse, Wisconsin, United States, 54601
      • Mayo Clinic Health System-Franciscan Healthcare
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center - University Hospital
    • Madison, Wisconsin, United States, 53718
      • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
    • Marinette, Wisconsin, United States, 54143
      • Aurora Bay Area Medical Group-Marinette
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Medical Center-Marshfield
    • Menomonee Falls, Wisconsin, United States, 53051
      • Froedtert Menomonee Falls Hospital
    • Mequon, Wisconsin, United States, 53097
      • Ascension Columbia Saint Mary's Hospital Ozaukee
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53209
      • Aurora Cancer Care-Milwaukee
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53233
      • Aurora Sinai Medical Center
    • Milwaukee, Wisconsin, United States, 53211
      • Ascension Columbia Saint Mary's Hospital - Milwaukee
    • Milwaukee, Wisconsin, United States, 53295
      • Zablocki Veterans Administration Medical Center
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Medical Center - Minocqua
    • Oak Creek, Wisconsin, United States, 53154
      • Drexel Town Square Health Center
    • Oshkosh, Wisconsin, United States, 54904
      • Ascension Mercy Hospital
    • Oshkosh, Wisconsin, United States, 54904
      • Vince Lombardi Cancer Clinic - Oshkosh
    • Racine, Wisconsin, United States, 53406
      • Aurora Cancer Care-Racine
    • Racine, Wisconsin, United States, 53405
      • Ascension All Saints Hospital
    • Rhinelander, Wisconsin, United States, 54501
      • Aspirus Cancer Care - James Beck Cancer Center
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Medical Center-Rice Lake
    • Sheboygan, Wisconsin, United States, 53081
      • Vince Lombardi Cancer Clinic-Sheboygan
    • Sheboygan, Wisconsin, United States, 53081
      • Saint Vincent Hospital Cancer Center at Sheboygan
    • Stevens Point, Wisconsin, United States, 54482
      • Marshfield Medical Center-River Region at Stevens Point
    • Stevens Point, Wisconsin, United States, 54481
      • Aspirus Cancer Care - Stevens Point
    • Sturgeon Bay, Wisconsin, United States, 54235-1495
      • Saint Vincent Hospital Cancer Center at Sturgeon Bay
    • Summit, Wisconsin, United States, 53066
      • Aurora Medical Center in Summit
    • Two Rivers, Wisconsin, United States, 54241
      • Vince Lombardi Cancer Clinic-Two Rivers
    • Wausau, Wisconsin, United States, 54401
      • Aspirus Regional Cancer Center
    • Wauwatosa, Wisconsin, United States, 53226
      • Aurora Cancer Care-Milwaukee West
    • Wauwatosa, Wisconsin, United States, 53226
      • Ascension Medical Group Southeast Wisconsin - Mayfair Road
    • West Allis, Wisconsin, United States, 53227
      • Aurora West Allis Medical Center
    • West Bend, Wisconsin, United States, 53095
      • Froedtert West Bend Hospital/Kraemer Cancer Center
    • Weston, Wisconsin, United States, 54476
      • Marshfield Medical Center - Weston
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Aspirus Cancer Care - Wisconsin Rapids

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• PRIOR TO STEP 1 REGISTRATION
• Pathologically proven diagnosis of adenocarcinoma of prostate cancer within 180 days prior to registration

• High-risk disease defined as having at least one or more of the following:

  • PSA > 20 ng/mL prior to starting ADT

    • Note: Patients receiving a 5-alpha reductase inhibitor (ex. finasteride) at the time of enrollment are eligible. The baseline PSA value should be doubled for PSAs taken while on 5-alpha reductase inhibitors and the medication should be discontinued prior to randomization but a washout period is not required
  • cT3a-T4 by digital exam or imaging (American Joint Committee on Cancer [AJCC] 8th edition [Ed.])
  • Gleason score of 8-10
  • Node positive by conventional imaging with a short axis of at least 1.0 cm

• Appropriate stage for study entry based on the following diagnostic workup:

  • History/physical examination within 120 days prior to registration;

  • Bone imaging within 120 days prior to registration;

    • Note: To be eligible, patient must have no definitive evidence of bone metastases (M0) on bone scan or sodium fluoride (NaF) PET within 120 days prior to registration (negative NaF PET/CT or negative Axumin or choline PET or negative fluciclovine, choline or prostate-specific membrane antigen (PSMA) PET within 120 days prior to registration is an acceptable substitute if they have been performed). Patients who have bone metastases established only fluciclovine, choline, or PSMA PET but not definitive on bone scan or NaF PET will still be eligible
  • CT or MRI of the pelvis within 120 days prior to registration (negative fluciclovine, choline, or PSMA PET within 120 days prior to registration is an acceptable substitute). As with bone staging, nodal staging for trial purposes will be based off of conventional imaging findings only
  • Patients with confirmed N1 metastases on conventional imaging (CT/MRI) as defined by >= 10 mm on short axis are eligible but will be automatically assigned to the intensification study. Patients who are positive by fluciclovine, choline, or PSMA PET (i.e. N1), but whose nodes do not meet traditional size criteria for positivity (i.e. they measure >= 10 mm on either the CT or MRI portion of the PET or on a dedicated CT or MRI) will not be considered N1 for the trial and will not automatically be assigned to the intensification study
• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 120 days prior to registration
• Hemoglobin >= 9.0 g/dL, independent of transfusion and/or growth factors (within 120 days prior to registration)
• Platelet count >= 100 x 10^3/uL independent of transfusion and/or growth factors (within 120 days prior to registration)

• Creatinine clearance (CrCl) >= 30 mL/min estimated by Cockcroft-Gault equation (within 120 days prior to registration)

  • For Black patients whose renal function is not considered adequate by Cockcroft-Gault formula, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) may be used for calculating creatinine clearance for trial eligibility
  • Either a CrCl >= 30 ml/min or calculated glomerular filtration rate (GFR) >= 30 will make a patient eligible

• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 120 days prior to registration)

  • Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject is eligible
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (within 120 days prior to registration)
• Serum albumin >= 3.0 g/dL (within 120 days prior to registration)
• The patient must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial and have a CD4 count >= 200 cells/microliter within 60 days prior to registration. Note: HIV testing is not required for eligibility for this protocol. Of note, for patients with HIV in the intensification trial randomized to apalutamide, highly active antiretroviral therapy (HAART) may need to be adjusted to medications that do not interact with apalutamide
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable after or on suppressive therapy within 60 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ or low-grade non-muscle invasive bladder cancer) who has been disease-free for less than 3 years must contact the principal investigator
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
• PRIOR TO STEP 2 RANDOMIZATION
• Confirmation of Decipher score
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load within 60 days prior. Note: Apalutamide may interfere with HCV drugs. Patients on HCV medications should alert their infectious diseases physician if they get randomized to apalutamide due to the possibility that apalutamide can affect the bioavailability of some HCV medications. HCV viral testing is not required for eligibility for this protocol
• For patients entering the Intensification Cohort ONLY: Patients must discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to Step 2 randomization

Exclusion Criteria:

• PRIOR TO STEP 1 REGISTRATION:
• Definitive radiologic evidence of metastatic disease outside of the pelvic nodes (M1a, M1b or M1c) on conventional imaging (i.e. bone scan, CT scan, MRI)
• Prior systemic chemotherapy within =< 3 years prior to registration; note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration
• Prior radical prostatectomy
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Current use of 5-alpha reductase inhibitor. NOTE: If the alpha reductase inhibitor is stopped prior to randomization the patient is eligible

• History of any of the following:

  • Seizure disorder
  • Current severe or unstable angina
  • New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
  • History of any condition that in the opinion of the investigator, would preclude participation in this study

• Evidence of any of the following at registration:

  • Active uncontrolled infection requiring IV antibiotics
  • Baseline severe hepatic impairment (Child Pugh Class C)
  • Inability to swallow oral pills
  • Any current condition that in the opinion of the investigator, would preclude participation in this study
• Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation (both luteinizing hormone-releasing hormone [LHRH] agonist and oral anti-androgen) is =< 60 days prior to registration; Please note: baseline PSA must be obtained prior to the start of any ADT
• PRIOR TO STEP 2 RANDOMIZATION:
• Evidence of known gastrointestinal disorder affecting absorption of oral medications at registration
• For patients entering the Intensification Cohort ONLY: Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] >= 160 mmHg or diastolic BP >= 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (de-intensification study); Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin, histrelin, or relugolix and bicalutamide or flutamide) for 24 months in the absence of disease progression or unacceptable toxicity. Patients undergo bone scan, PET scan, CT scan, and MRI at screening and as clinically indicated and may optionally undergo blood sample collection throughout the study.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Energy Type; Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Procedure: Bone Scan; Undergo bone scan; Other Names: Bone Scintigraphy; Procedure: Magnetic Resonance Elastography; Undergo MRI; Other Names: MRE; Drug: Degarelix; Given degarelix; Other Names: Firmagon; FE200486; FE 200486; ASP3550; ASP 3550; ASP-3550; FE-200486; Drug: Goserelin; Given goserelin; Other Names: ICI-118630; Drug: Histrelin; Given histrelin; Drug: Leuprolide; Given leuprolide; Other Names: Leuprorelin; Drug: Relugolix; Given relugolix; Other Names: TAK-385; Orgovyx; N-(4-(1-((2,6-Difluorophenyl)methyl)-5-((dimethylamino)methyl)-1,2,3,4-tetrahydro-3-(6-methoxy-3-pyridazinyl)-2,4-dioxothieno(2,3-d)pyrimidin-6-yl)phenyl)-N'-methoxyurea; TAK 385; Relumina; TAK385; Drug: Triptorelin; Given triptorelin; Other Names: 6-D-Tryptophan-LH-RH; 6-D-Tryptophanluteinizing Hormone-releasing Factor; AY-25650; CL-118,532; Detryptoreline; AY25650; CL118532; AY 25650; CL 118532; CL-118532; Drug: Bicalutamide; Given bicalutamide; Other Names: Casodex; Cosudex; ICI 176,334; ICI 176334; Cassotide; Utamide; Drug: Buserelin; Given buserelin; Other Names: 6-[O-(1,1-Dimethylethyl)-D-serine]-9-(N-ethyl-L-prolinamide)-10-deglycinamide-luteinizing Hormone-releasing Factor (Pig); BSRL; Busereline; Etilamide; HOE 766; ICI 123215; S74-6766; HOE-766; HOE766; ICI-123215; ICI123215; S74 6766; S746766; Tiloryth; Drug: Flutamide; Given flutamide; Other Names: Apimid; Cebatrol; Chimax; Cytomid; Drogenil; Euflex; Eulexine; Flucinom; Flucinome; Flugerel; Fluken; Flulem; FLUT; Fluta-Gry; Flutabene; Flutacan; Flutamex; Flutamin; Flutan; Flutaplex; Fugerel; Grisetin; Niftolide; Oncosal; Profamid; Propanamide, 2-Methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)-; Prostacur; Prostadirex; Prostica; Prostogenat; Sch 13521; Tafenil; Tecnoflut; Testotard; 4'-Nitro-3'-trifluoromethylisobutyranilide
Experimental: Arm II (de-intensification study); Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin, histrelin, or relugolix and bicalutamide or flutamide) for 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo bone scan, PET scan, CT scan, and MRI at screening and as clinically indicated and may optionally undergo blood sample collection throughout the study.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Energy Type; Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Procedure: Bone Scan; Undergo bone scan; Other Names: Bone Scintigraphy; Procedure: Magnetic Resonance Elastography; Undergo MRI; Other Names: MRE; Drug: Degarelix; Given degarelix; Other Names: Firmagon; FE200486; FE 200486; ASP3550; ASP 3550; ASP-3550; FE-200486; Drug: Goserelin; Given goserelin; Other Names: ICI-118630; Drug: Histrelin; Given histrelin; Drug: Leuprolide; Given leuprolide; Other Names: Leuprorelin; Drug: Relugolix; Given relugolix; Other Names: TAK-385; Orgovyx; N-(4-(1-((2,6-Difluorophenyl)methyl)-5-((dimethylamino)methyl)-1,2,3,4-tetrahydro-3-(6-methoxy-3-pyridazinyl)-2,4-dioxothieno(2,3-d)pyrimidin-6-yl)phenyl)-N'-methoxyurea; TAK 385; Relumina; TAK385; Drug: Triptorelin; Given triptorelin; Other Names: 6-D-Tryptophan-LH-RH; 6-D-Tryptophanluteinizing Hormone-releasing Factor; AY-25650; CL-118,532; Detryptoreline; AY25650; CL118532; AY 25650; CL 118532; CL-118532; Drug: Bicalutamide; Given bicalutamide; Other Names: Casodex; Cosudex; ICI 176,334; ICI 176334; Cassotide; Utamide; Drug: Buserelin; Given buserelin; Other Names: 6-[O-(1,1-Dimethylethyl)-D-serine]-9-(N-ethyl-L-prolinamide)-10-deglycinamide-luteinizing Hormone-releasing Factor (Pig); BSRL; Busereline; Etilamide; HOE 766; ICI 123215; S74-6766; HOE-766; HOE766; ICI-123215; ICI123215; S74 6766; S746766; Tiloryth; Drug: Flutamide; Given flutamide; Other Names: Apimid; Cebatrol; Chimax; Cytomid; Drogenil; Euflex; Eulexine; Flucinom; Flucinome; Flugerel; Fluken; Flulem; FLUT; Fluta-Gry; Flutabene; Flutacan; Flutamex; Flutamin; Flutan; Flutaplex; Fugerel; Grisetin; Niftolide; Oncosal; Profamid; Propanamide, 2-Methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)-; Prostacur; Prostadirex; Prostica; Prostogenat; Sch 13521; Tafenil; Tecnoflut; Testotard; 4'-Nitro-3'-trifluoromethylisobutyranilide
Active Comparator: Arm III (intensification study); Patients undergo RT over 2-11 weeks and receive ADT as in Arm I. Patients undergo bone scan, PET scan, CT scan, and MRI at screening and as clinically indicated and may optionally undergo blood sample collection throughout the study.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Energy Type; Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Procedure: Bone Scan; Undergo bone scan; Other Names: Bone Scintigraphy; Procedure: Magnetic Resonance Elastography; Undergo MRI; Other Names: MRE; Drug: Degarelix; Given degarelix; Other Names: Firmagon; FE200486; FE 200486; ASP3550; ASP 3550; ASP-3550; FE-200486; Drug: Goserelin; Given goserelin; Other Names: ICI-118630; Drug: Histrelin; Given histrelin; Drug: Leuprolide; Given leuprolide; Other Names: Leuprorelin; Drug: Relugolix; Given relugolix; Other Names: TAK-385; Orgovyx; N-(4-(1-((2,6-Difluorophenyl)methyl)-5-((dimethylamino)methyl)-1,2,3,4-tetrahydro-3-(6-methoxy-3-pyridazinyl)-2,4-dioxothieno(2,3-d)pyrimidin-6-yl)phenyl)-N'-methoxyurea; TAK 385; Relumina; TAK385; Drug: Triptorelin; Given triptorelin; Other Names: 6-D-Tryptophan-LH-RH; 6-D-Tryptophanluteinizing Hormone-releasing Factor; AY-25650; CL-118,532; Detryptoreline; AY25650; CL118532; AY 25650; CL 118532; CL-118532; Drug: Bicalutamide; Given bicalutamide; Other Names: Casodex; Cosudex; ICI 176,334; ICI 176334; Cassotide; Utamide; Drug: Buserelin; Given buserelin; Other Names: 6-[O-(1,1-Dimethylethyl)-D-serine]-9-(N-ethyl-L-prolinamide)-10-deglycinamide-luteinizing Hormone-releasing Factor (Pig); BSRL; Busereline; Etilamide; HOE 766; ICI 123215; S74-6766; HOE-766; HOE766; ICI-123215; ICI123215; S74 6766; S746766; Tiloryth; Drug: Flutamide; Given flutamide; Other Names: Apimid; Cebatrol; Chimax; Cytomid; Drogenil; Euflex; Eulexine; Flucinom; Flucinome; Flugerel; Fluken; Flulem; FLUT; Fluta-Gry; Flutabene; Flutacan; Flutamex; Flutamin; Flutan; Flutaplex; Fugerel; Grisetin; Niftolide; Oncosal; Profamid; Propanamide, 2-Methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)-; Prostacur; Prostadirex; Prostica; Prostogenat; Sch 13521; Tafenil; Tecnoflut; Testotard; 4'-Nitro-3'-trifluoromethylisobutyranilide
Experimental: Arm IV (intensification study); Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin, histrelin, or relugolix) for 24 months in the absence of disease progression or unacceptable toxicity. Patients also receive apalutamide PO QD. Treatment repeats every 90 days for up to 8 cycles (24 months) in the absence of disease progression or unacceptable toxicity. Patients undergo bone scan, PET scan, CT scan, and MRI at screening and as clinically indicated and may optionally undergo blood sample collection throughout the study.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Energy Type; Drug: Apalutamide; Given PO; Other Names: ARN-509; JNJ-56021927; ARN 509; ARN509; Erleada; JNJ 56021927; Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Procedure: Bone Scan; Undergo bone scan; Other Names: Bone Scintigraphy; Procedure: Magnetic Resonance Elastography; Undergo MRI; Other Names: MRE; Drug: Degarelix; Given degarelix; Other Names: Firmagon; FE200486; FE 200486; ASP3550; ASP 3550; ASP-3550; FE-200486; Drug: Goserelin; Given goserelin; Other Names: ICI-118630; Drug: Histrelin; Given histrelin; Drug: Leuprolide; Given leuprolide; Other Names: Leuprorelin; Drug: Relugolix; Given relugolix; Other Names: TAK-385; Orgovyx; N-(4-(1-((2,6-Difluorophenyl)methyl)-5-((dimethylamino)methyl)-1,2,3,4-tetrahydro-3-(6-methoxy-3-pyridazinyl)-2,4-dioxothieno(2,3-d)pyrimidin-6-yl)phenyl)-N'-methoxyurea; TAK 385; Relumina; TAK385; Drug: Triptorelin; Given triptorelin; Other Names: 6-D-Tryptophan-LH-RH; 6-D-Tryptophanluteinizing Hormone-releasing Factor; AY-25650; CL-118,532; Detryptoreline; AY25650; CL118532; AY 25650; CL 118532; CL-118532; Drug: Buserelin; Given buserelin; Other Names: 6-[O-(1,1-Dimethylethyl)-D-serine]-9-(N-ethyl-L-prolinamide)-10-deglycinamide-luteinizing Hormone-releasing Factor (Pig); BSRL; Busereline; Etilamide; HOE 766; ICI 123215; S74-6766; HOE-766; HOE766; ICI-123215; ICI123215; S74 6766; S746766; Tiloryth

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metastasis-free survival (MFS)	Assessed based on conventional imaging. MFS will be estimated using the Kaplan-Meier method (Kaplan 1958).	From randomization to the date of detection of distant metastasis on standard imaging or date of death from any cause, assessed up to 13 years
Sexual quality of life (De-intensification study)	Measured by Expanded Prostate Cancer Index Composite-26 sexual domain	Up to 13 years
Hormonal quality of life (De-intensification study)	Measured by EPIC-26 hormonal domain	Up to 13 years
Fatigue (Intensification study)	Measured by Patient Reported Outcomes Measurement Information Systems (PROMIS) Fatigue short form (SF)	Up to 13 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MFS	Assessed based on standard or molecular, if available, imaging. MFS will be estimated using the Kaplan-Meier method (Kaplan 1958)	From randomization to the date of detection of distant metastasis on standard imaging or date of death from any cause, assessed up to 13 years
Overall survival	Will be estimated using the Kaplan-Meier method and treatment arms compared using the stratified log-rank test (Kaplan 1958).	From the date of randomization to the date of death or last known follow-up date, with patients alive at the last known follow-up time treated as censored, assessed up to 13 years
Prostate cancer specific mortality (PCSM)		From the date of randomization to the date of prostate cancer death, assessed up to 13 years
Prostate specific antigen (PSA) failure-free survival with non-castrate testosterone and no additional therapies	PSA failure-free survival will be estimated using the Kaplan-Meier method and treatment arms compared using the stratified log-rank test (Kaplan 1958).	From the date of randomization to the date event, or death or censored at the last known follow-up date, assessed up to 13 years
Time to testosterone recovery	Defined as testosterone that is non-castrate.	Up to 13 years
Time to PSA failure or salvage therapy		Up to 13 years
Testosterone levels at the time of PSA failure and metastases		Up to 13 years
Incidence of adverse events	Measured by the Common Terminology Criteria for Adverse Events (CTCAE ) version (v) 5.0 and Patient Reported Outcomes (PRO)-CTCAE.	Up to 13 years
Depression (De-intensification study)	Measured by the PROMIS Depression	Up to 13 years
Depression (Intensification study)	Measured by the PROMIS Depression	Up to 13 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardio-metabolic markers including body mass index and waist circumference		Up to 13 years
Machine learning/artificial intelligence algorithm		Up to 13 years
Bowel and urinary quality of life (De-intensification study)	Measured by EPIC-26 bowel and urinary domains.	Up to 13 years
Cognition (De-intensification study)	Measured by the Functional Assessment of Chronic Illness Therapy-Cognition (FACIT-Cog) perceived cognitive abilities subscale.	Up to 13 years
Cognition (Intensification study)	Measured by the FACIT-Cog perceived cognitive abilities subscale.	Up to 13 years
Impact of PET use	Measured by the proportion of times each type of imaging was used.	Up to 13 years
Fatigue (De-intensification study)	Measured by PROMIS- Fatigue Short Form (SF)	Up to 13 years
Sexual, hormonal, bowel, and urinary quality of life (Intensification study)	Measured by EPIC-26	Up to 13 years
Primary outcome treatment effect by sex	Estimates of the primary outcome treatment effect and the corresponding 95% confidence intervals (CIs) by sex.	Up to 13 years
Primary outcome treatment effect by race	Estimates of the primary outcome treatment effect and the corresponding 95% CIs by race.	Up to 13 years
Primary outcome treatment effect by ethnicity	Estimates of the primary outcome treatment effect and the corresponding 95% CIs by ethnicity.	Up to 13 years

Collaborators and Investigators

• Sponsor: NRG Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Paul L Nguyen, NRG Oncology

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2021
• Primary Completion (Estimated): December 31, 2033
• Study Completion (Estimated): December 31, 2033

Study Registration Dates

• First Submitted: August 7, 2020
• First Submitted That Met QC Criteria: August 11, 2020
• First Posted (Actual): August 14, 2020

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Organic Chemicals; Investigative Techniques; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hydrocarbons; Hydrocarbons, Cyclic; Physical Phenomena; Carboxylic Acids; Hydroxy Acids; Hydrocarbons, Aromatic; Anilides; Amides; Aniline Compounds; Amines; Phenols; Benzene Derivatives; Chemistry Techniques, Analytical; Spectrum Analysis; Acids, Carbocyclic; Benzoates; Salicylates; Hydroxybenzoates; Gonadotropin-Releasing Hormone; Salicylic Acid; Leuprolide; Goserelin; Triptorelin Pamoate; Flutamide; Buserelin; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; relugolix; Radiotherapy; Radiation; Specimen Handling; Magnetic Resonance Spectroscopy; apalutamide; bicalutamide; histrelin
• Other Study ID Numbers: NRG-GU009 (Other Identifier: CTEP); U10CA180868 (U.S. NIH Grant/Contract); NCI-2020-04705 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No