De-intensified Radiation Therapy With Chemotherapy (Cisplatin) or Immunotherapy (Nivolumab) in Treating Patients With Early-Stage, HPV-Positive, Non-Smoking Associated Oropharyngeal Cancer

April 23, 2024 updated by: National Cancer Institute (NCI)

A Randomized Phase II/III Trial of De-Intensified Radiation Therapy for Patients With Early-Stage, P16-Positive, Non-Smoking Associated Oropharyngeal Cancer

This phase II/III trial studies how well a reduced dose of radiation therapy works with nivolumab compared to cisplatin in treating patients with human papillomavirus (HPV)-positive oropharyngeal cancer that is early in its growth and may not have spread to other parts of the body (early-stage), and is not associated with smoking. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial is being done to see if a reduced dose of radiation therapy and nivolumab works as well as standard dose radiation therapy and cisplatin in treating patients with oropharyngeal cancer.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To demonstrate non-inferiority in terms of progression-free survival (PFS) of concurrent reduced-dose radiation therapy (RT) with cisplatin or concurrent reduced-dose radiation therapy with nivolumab to the current standard of care (standard-dose RT with cisplatin). (Phase II) (Arm 2 [concurrent reduced-dose RT with cisplatin] was dropped after interim futility analysis in phase II.) II. To demonstrate non-inferiority in terms of progression-free survival (PFS) of concurrent reduced-dose radiation therapy (RT) with nivolumab to the current standard of care (standard-dose RT with cisplatin). (Phase II) III. To demonstrate co-primary endpoints of non-inferiority of PFS and superiority of quality of life (QOL) as measured by the MD Anderson Dysphagia Inventory (MDADI) of concurrent reduced-dose radiation with cisplatin or concurrent reduced-dose radiation with nivolumab to the current standard of care (standard-dose RT with cisplatin). (Phase III) (Arm 2 [concurrent reduced-dose RT with cisplatin] was dropped after interim futility analysis in phase II.) IV. To demonstrate co-primary endpoints of non-inferiority of PFS and superiority of quality of life (QOL) as measured by the MD Anderson Dysphagia Inventory [MDADI] of concurrent reduced-dose radiation with nivolumab to the current standard of care (standard-dose RT with cisplatin). (Phase III)

SECONDARY OBJECTIVES:

I. To compare patterns of failure (local and regional relapse versus distant) and overall survival between the experimental arm and the control arm.

II. To assess long term PFS, overall survival, and toxicity between the experimental arm and the control arm.

III. To determine acute and late toxicity profiles as measured by the Common Terminology Criteria for Adverse Events (CTCAE).

IV. To explore the symptomatic adverse events (AEs) for tolerability of each treatment arm as measured by the Patient-Reported Outcomes (PRO)-CTCAE.

V. To compare changes in patient-reported outcomes (Hearing Handicap Inventory for Adults-Screening [HHIA-S], European Organization for Research and Treatment of Cancer [EORTC]-Quality of Life Questionnaire [QLQ]30) between the experimental arm and the control arm.

VI. To assess the association of fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) at baseline with locoregional control and PFS.

VII. To estimate the negative predictive value of the 12-14 weeks post-radiation therapy (RT) FDG-PET/CT in terms of locoregional control rates and PFS rates at 1 and 2 years.

EXPLORATORY OBJECTIVES:

I. To collect blood and tissue specimens for future translation research. II. To optimize radiotherapy treatment plan quality assurance methodology for radiotherapy planning and imaging.

III. To compare changes in patient-reported outcomes (European Quality of Life Five Dimension Five Level Scale [EQ-5D-5L]) between the experimental arm and the control arm.

IV. To collect Modified Barium Swallow (MBS) data for future review and analysis.

OUTLINE:

PHASE II: Patients are randomized to 1 of 3 arms.

ARM I: Patients undergo intensity modulated radiation therapy (IMRT) or image-guided radiation therapy (IGRT) over 6 fractions per week and receive cisplatin intravenously (IV) over 30-60 minutes on days 1 and 22. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients receive fludeoxyglucose F-18 (FDG) and undergo positron emission tomography (PET)/computed tomography (CT) or CT during screening and during follow up, and undergo magnetic resonance imaging (MRI) during follow up. Patients may also undergo tissue biopsy and blood sample collection throughout the study.

ARM II (CLOSED TO ACCRUAL 03-FEB-2023): Patients undergo reduced dose IMRT or IGRT once daily (QD) over 5 fractions per week and receive cisplatin IV over 30-60 minutes on days 1 and 22. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients receive FDG and undergo PET/CT or CT during screening and during follow up, and undergo MRI during follow up. Patients may also undergo tissue biopsy and blood sample collection throughout the study.

ARM III: Beginning 1 week prior to radiation, patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks (14 days) for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo reduced dose IMRT or IGRT over 6 fractions per week for 5 weeks in the absence of disease progression or unacceptable toxicity. Patients receive FDG and undergo PET/CT or CT during screening and during follow up, and undergo MRI during follow up. Patients may also undergo tissue biopsy and blood sample collection throughout the study.

PHASE III: Patients are randomized to Arm I and/or Arm III.

After completion of study treatment, patients are followed up at 12-14 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Study Type

Interventional

Enrollment (Estimated)

590

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • University Health Network-Princess Margaret Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham Cancer Center
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Banner MD Anderson Cancer Center
      • Tucson, Arizona, United States, 85719
        • Banner University Medical Center - Tucson
      • Tucson, Arizona, United States, 85719
        • University of Arizona Cancer Center-North Campus
    • California
      • Antioch, California, United States, 94531
        • Kaiser Permanente-Deer Valley Medical Center
      • Arroyo Grande, California, United States, 93420
        • PCR Oncology
      • Auburn, California, United States, 95602
        • Sutter Auburn Faith Hospital
      • 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
      • Beverly Hills, California, United States, 90211
        • Tower Cancer Research Foundation
      • Cameron Park, California, United States, 95682
        • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
      • 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
      • Fresno, California, United States, 93720
        • Kaiser Permanente-Fresno
      • Fresno, California, United States, 93720
        • Fresno Cancer Center
      • Irvine, California, United States, 92618
        • City of Hope at Irvine Lennar
      • 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, 95356
        • Kaiser Permanente-Modesto
      • Mountain View, California, United States, 94040
        • Palo Alto Medical Foundation-Camino Division
      • Oakland, California, United States, 94611
        • Kaiser Permanente-Oakland
      • Oakland, California, United States, 94611
        • Kaiser Permanente Oakland-Broadway
      • Palo Alto, California, United States, 94304
        • Stanford Cancer Institute Palo Alto
      • Palo Alto, California, United States, 94301
        • Palo Alto Medical Foundation Health Care
      • Rancho Cordova, California, United States, 95670
        • Kaiser Permanente-Rancho Cordova Cancer Center
      • Redwood City, California, United States, 94063
        • Kaiser Permanente- Marshall Medical Offices
      • Richmond, California, United States, 94801
        • Kaiser Permanente-Richmond
      • Rohnert Park, California, United States, 94928
        • Rohnert Park Cancer Center
      • Roseville, California, United States, 95678
        • The Permanente Medical Group-Roseville Radiation Oncology
      • Roseville, California, United States, 95661
        • Kaiser Permanente-Roseville
      • Roseville, California, United States, 95661
        • Sutter Cancer Centers Radiation Oncology Services-Roseville
      • Roseville, California, United States, 95661
        • Sutter Roseville Medical Center
      • 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
      • Sacramento, California, United States, 95823
        • South Sacramento Cancer Center
      • San Diego, California, United States, 92134
        • Naval Medical Center -San Diego
      • San Diego, California, United States, 92103
        • UC San Diego Medical Center - Hillcrest
      • 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 Luis Obispo, California, United States, 93401
        • Pacific Central Coast Health Center-San Luis Obispo
      • San Rafael, California, United States, 94903
        • Kaiser San Rafael-Gallinas
      • 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 Cancer Treatment Center
      • South San Francisco, California, United States, 94080
        • Kaiser Permanente-South San Francisco
      • Stockton, California, United States, 95210
        • Kaiser Permanente-Stockton
      • Sunnyvale, California, United States, 94086
        • Palo Alto Medical Foundation-Sunnyvale
      • 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
      • Upland, California, United States, 91786
        • City of Hope Upland
      • Vacaville, California, United States, 95688
        • Kaiser Permanente Medical Center-Vacaville
      • Vallejo, California, United States, 94589
        • Kaiser Permanente-Vallejo
      • Walnut Creek, California, United States, 94596
        • Kaiser Permanente-Walnut Creek
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Rocky Mountain Regional VA Medical Center
      • 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, 80907
        • Rocky Mountain Cancer Centers-Penrose
      • Colorado Springs, Colorado, United States, 80920
        • Memorial Hospital North
      • Denver, Colorado, United States, 80210
        • Porter Adventist Hospital
      • Fort Collins, Colorado, United States, 80524
        • Poudre Valley Hospital
      • Fort Collins, Colorado, United States, 80528
        • Cancer Care and Hematology-Fort Collins
      • Greeley, Colorado, United States, 80631
        • UCHealth Greeley Hospital
      • Littleton, Colorado, United States, 80122
        • Littleton Adventist Hospital
      • Loveland, Colorado, United States, 80538
        • Medical Center of the Rockies
      • Parker, Colorado, United States, 80138
        • Parker Adventist Hospital
    • Connecticut
      • Hartford, Connecticut, United States, 06102
        • Hartford Hospital
    • Delaware
      • Newark, Delaware, United States, 19713
        • Helen F Graham Cancer Center
      • Newark, Delaware, United States, 19713
        • Delaware Clinical and Laboratory Physicians PA
      • Newark, Delaware, United States, 19713
        • Medical Oncology Hematology Consultants PA
      • Newark, Delaware, United States, 19718
        • Christiana Care Health System-Christiana Hospital
    • Florida
      • Coral Gables, Florida, United States, 33146
        • UM Sylvester Comprehensive Cancer Center at Coral Gables
      • Coral Springs, Florida, United States, 33065
        • UM Sylvester Comprehensive Cancer Center at Coral Springs
      • Deerfield Beach, Florida, United States, 33442
        • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
      • Jupiter, Florida, United States, 33458
        • Jupiter Medical Center
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Miami, Florida, United States, 33176
        • Miami Cancer Institute
      • Miami, Florida, United States, 33176
        • UM Sylvester Comprehensive Cancer Center at Kendall
      • Orlando, Florida, United States, 32806
        • Orlando Health Cancer Institute
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
      • Tampa, Florida, United States, 33607
        • Moffitt Cancer Center-International Plaza
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center - McKinley Campus
      • Wesley Chapel, Florida, United States, 33544
        • Moffitt Cancer Center at Wesley Chapel
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Emory University Hospital Midtown
      • Atlanta, Georgia, United States, 30303
        • Grady Health System
    • Hawaii
      • 'Aiea, Hawaii, United States, 96701
        • Pali Momi Medical Center
      • 'Aiea, Hawaii, United States, 96701
        • Hawaii Cancer Care - Westridge
      • 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
        • Hawaii Cancer Care Inc-Liliha
      • Honolulu, Hawaii, United States, 96817
        • Kuakini Medical Center
      • Honolulu, Hawaii, United States, 96817
        • Queen's Cancer Center - Kuakini
      • Honolulu, Hawaii, United States, 96826
        • Kapiolani Medical Center for Women and Children
      • Honolulu, Hawaii, United States, 96819
        • Kaiser Permanente Moanalua Medical Center
      • Lihue, Hawaii, United States, 96766
        • Wilcox Memorial Hospital and Kauai Medical Clinic
    • Idaho
      • Boise, Idaho, United States, 83706
        • Saint Alphonsus Cancer Care Center-Boise
      • Boise, Idaho, United States, 83712
        • Saint Luke's Cancer Institute - Boise
      • Caldwell, Idaho, United States, 83605
        • Saint Alphonsus Cancer Care Center-Caldwell
      • Fruitland, Idaho, United States, 83619
        • Saint Luke's Cancer Institute - Fruitland
      • Meridian, Idaho, United States, 83642
        • Saint Luke's Cancer Institute - Meridian
      • Nampa, Idaho, United States, 83686
        • Saint Luke's Cancer Institute - Nampa
      • Nampa, Idaho, United States, 83687
        • Saint Alphonsus Cancer Care Center-Nampa
      • Twin Falls, Idaho, United States, 83301
        • Saint Luke's Cancer Institute - Twin Falls
    • Illinois
      • 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
      • Centralia, Illinois, United States, 62801
        • Centralia Oncology Clinic
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60657
        • Advocate Illinois Masonic Medical Center
      • Crystal Lake, Illinois, United States, 60014
        • AMG Crystal Lake - Oncology
      • DeKalb, Illinois, United States, 60115
        • Northwestern Medicine Cancer Center Kishwaukee
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
      • Decatur, Illinois, United States, 62526
        • Cancer Care Specialists of Illinois - Decatur
      • 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
      • Eureka, Illinois, United States, 61530
        • Illinois CancerCare-Eureka
      • Evanston, Illinois, United States, 60201
        • NorthShore University HealthSystem-Evanston Hospital
      • Galesburg, Illinois, United States, 61401
        • Western Illinois Cancer Treatment Center
      • Galesburg, Illinois, United States, 61401
        • Illinois CancerCare-Galesburg
      • Geneva, Illinois, United States, 60134
        • Northwestern Medicine Cancer Center Delnor
      • Glenview, Illinois, United States, 60026
        • NorthShore University HealthSystem-Glenbrook Hospital
      • Highland Park, Illinois, United States, 60035
        • NorthShore University HealthSystem-Highland Park Hospital
      • Kewanee, Illinois, United States, 61443
        • Illinois CancerCare-Kewanee Clinic
      • Macomb, Illinois, United States, 61455
        • Illinois CancerCare-Macomb
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
      • O'Fallon, Illinois, United States, 62269
        • Cancer Care Center of O'Fallon
      • Ottawa, Illinois, United States, 61350
        • Illinois CancerCare-Ottawa Clinic
      • 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
      • Princeton, Illinois, United States, 61356
        • Illinois CancerCare-Princeton
      • Rockford, Illinois, United States, 61114
        • SwedishAmerican Regional Cancer Center/ACT
      • Shiloh, Illinois, United States, 62269
        • Memorial Hospital East
      • Springfield, Illinois, United States, 62781
        • Memorial Medical Center
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University School of Medicine
      • Springfield, Illinois, United States, 62702
        • Springfield Clinic
      • Warrenville, Illinois, United States, 60555
        • Northwestern Medicine Cancer Center Warrenville
      • Washington, Illinois, United States, 61571
        • Illinois CancerCare - Washington
    • Indiana
      • Carmel, Indiana, United States, 46032
        • IU Health North Hospital
      • Indianapolis, Indiana, United States, 46202
        • Indiana University/Melvin and Bren Simon Cancer Center
      • Indianapolis, Indiana, United States, 46202
        • Sidney and Lois Eskenazi Hospital
    • Iowa
      • Clive, Iowa, United States, 50325
        • Mercy Cancer Center-West Lakes
      • Clive, Iowa, United States, 50325
        • Medical Oncology and Hematology Associates-West Des Moines
      • Creston, Iowa, United States, 50801
        • Greater Regional Medical Center
      • Des Moines, Iowa, United States, 50309
        • Iowa Methodist Medical Center
      • Des Moines, Iowa, United States, 50314
        • Mercy Medical Center - Des Moines
      • Des Moines, Iowa, United States, 50309
        • Medical Oncology and Hematology Associates-Des Moines
      • Des Moines, Iowa, United States, 50314
        • Broadlawns Medical Center
      • Des Moines, Iowa, United States, 50314
        • Mission Cancer and Blood - Laurel
      • Des Moines, Iowa, United States, 50316
        • Iowa Lutheran Hospital
      • West Des Moines, Iowa, United States, 50266-7700
        • Methodist West Hospital
      • West Des Moines, Iowa, United States, 50266
        • Mercy Medical Center-West Lakes
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center
      • Lawrence, Kansas, United States, 66044
        • Lawrence Memorial Hospital
      • Olathe, Kansas, United States, 66061
        • Olathe Health Cancer Center
      • 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
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky/Markey Cancer Center
      • Louisville, Kentucky, United States, 40202
        • Norton Hospital Pavilion and Medical Campus
      • Louisville, Kentucky, United States, 40202
        • The James Graham Brown Cancer Center at University of Louisville
      • Louisville, Kentucky, United States, 40241
        • Norton Brownsboro Hospital and Medical Campus
      • Louisville, Kentucky, United States, 40202
        • Jewish Hospital
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70805
        • LSU Health Baton Rouge-North Clinic
      • Baton Rouge, Louisiana, United States, 70809
        • Louisiana Hematology Oncology Associates LLC
      • Baton Rouge, Louisiana, United States, 70809
        • Mary Bird Perkins Cancer Center
      • Baton Rouge, Louisiana, United States, 70809
        • Our Lady of the Lake Physicians Group - Medical Oncology
      • Metairie, Louisiana, United States, 70006
        • East Jefferson General Hospital
    • Maine
      • Bath, Maine, United States, 04530
        • MaineHealth Coastal Cancer Treatment Center
      • Biddeford, Maine, United States, 04005
        • MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford
      • Portland, Maine, United States, 04102
        • Maine Medical Center-Bramhall Campus
      • Rockport, Maine, United States, 04856
        • Penobscot Bay Medical Center
      • Sanford, Maine, United States, 04073
        • MaineHealth Cancer Care Center of York County
      • Sanford, Maine, United States, 04073
        • MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford
      • Scarborough, Maine, United States, 04074
        • Maine Medical Center- Scarborough Campus
      • South Portland, Maine, United States, 04106
        • Maine Medical Partners - South Portland
    • Maryland
      • Baltimore, Maryland, United States, 21204
        • Greater Baltimore Medical Center
      • Baltimore, Maryland, United States, 21201
        • University of Maryland/Greenebaum Cancer Center
      • Bel Air, Maryland, United States, 21014
        • UM Upper Chesapeake Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • Saint Joseph Mercy Hospital
      • Bay City, Michigan, United States, 48706
        • McLaren Cancer Institute-Bay City
      • Brighton, Michigan, United States, 48114
        • Saint Joseph Mercy Brighton
      • Brighton, Michigan, United States, 48114
        • Trinity Health IHA Medical Group Hematology Oncology - Brighton
      • Brownstown, Michigan, United States, 48183
        • Henry Ford Cancer Institute-Downriver
      • Canton, Michigan, United States, 48188
        • Saint Joseph Mercy Canton
      • Canton, Michigan, United States, 48188
        • Trinity Health IHA Medical Group Hematology Oncology - Canton
      • Caro, Michigan, United States, 48723
        • Caro Cancer Center
      • Chelsea, Michigan, United States, 48118
        • Saint Joseph Mercy Chelsea
      • Chelsea, Michigan, United States, 48118
        • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
      • Clarkston, Michigan, United States, 48346
        • McLaren Cancer Institute-Clarkston
      • Clinton Township, Michigan, United States, 48038
        • Henry Ford Macomb Hospital-Clinton Township
      • Dearborn, Michigan, United States, 48126
        • Henry Ford Medical Center-Fairlane
      • 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
      • Flint, Michigan, United States, 48532
        • McLaren Cancer Institute-Flint
      • Flint, Michigan, United States, 48532
        • Singh and Arora Hematology Oncology PC
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health at Butterworth Campus
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital at Spectrum Health
      • Grand Rapids, Michigan, United States, 49503
        • Trinity Health Grand Rapids Hospital
      • Lansing, Michigan, United States, 48912
        • Mid-Michigan Physicians-Lansing
      • 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
      • Marlette, Michigan, United States, 48453
        • Saint Mary's Oncology/Hematology Associates of Marlette
      • Mount Clemens, Michigan, United States, 48043
        • McLaren Cancer Institute-Macomb
      • Niles, Michigan, United States, 49120
        • Corewell Health Lakeland Hospitals - Niles Hospital
      • Novi, Michigan, United States, 48377
        • Henry Ford Medical Center-Columbus
      • Petoskey, Michigan, United States, 49770
        • McLaren Cancer Institute-Northern Michigan
      • Port Huron, Michigan, United States, 48060
        • McLaren-Port Huron
      • Saginaw, Michigan, United States, 48601
        • Ascension Saint Mary's Hospital
      • Saginaw, Michigan, United States, 48604
        • Oncology Hematology Associates of Saginaw Valley PC
      • Saint Joseph, Michigan, United States, 49085
        • Lakeland Medical Center Saint Joseph
      • Saint Joseph, Michigan, United States, 49085
        • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
      • Shelby, Michigan, United States, 48315
        • Henry Ford Macomb Health Center - Shelby Township
      • Tawas City, Michigan, United States, 48764
        • Ascension Saint Joseph Hospital
      • West Bloomfield, Michigan, United States, 48322
        • Henry Ford West Bloomfield Hospital
      • West Branch, Michigan, United States, 48661
        • Saint Mary's Oncology/Hematology Associates of West Branch
      • 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
      • Bemidji, Minnesota, United States, 56601
        • Sanford Joe Lueken Cancer Center
      • Brainerd, Minnesota, United States, 56401
        • Essentia Health Saint Joseph's Medical Center
      • Deer River, Minnesota, United States, 56636
        • Essentia Health - Deer River Clinic
      • Duluth, Minnesota, United States, 55805
        • Essentia Health Cancer Center
      • Duluth, Minnesota, United States, 55805
        • Essentia Health Saint Mary's Medical Center
      • Duluth, Minnesota, United States, 55805
        • Miller-Dwan Hospital
      • Hibbing, Minnesota, United States, 55746
        • Essentia Health Hibbing Clinic
      • Saint Cloud, Minnesota, United States, 56303
        • Coborn Cancer Center at Saint Cloud Hospital
      • Sandstone, Minnesota, United States, 55072
        • Essentia Health Sandstone
      • Virginia, Minnesota, United States, 55792
        • Essentia Health Virginia Clinic
    • Missouri
      • Cape Girardeau, Missouri, United States, 63703
        • Saint Francis Medical 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
        • Delbert Day Cancer Institute at PCRMC
      • Rolla, Missouri, United States, 65401
        • Mercy Clinic-Rolla-Cancer and Hematology
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, United States, 63129
        • Siteman Cancer Center-South County
      • Saint Peters, Missouri, United States, 63376
        • Siteman Cancer Center at Saint Peters Hospital
      • Springfield, Missouri, United States, 65804
        • Mercy Hospital Springfield
    • Montana
      • Bozeman, Montana, United States, 59715
        • Bozeman Deaconess Hospital
      • Great Falls, Montana, United States, 59405
        • Benefis Healthcare- Sletten Cancer Institute
    • Nebraska
      • Kearney, Nebraska, United States, 68847
        • CHI Health Good Samaritan
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • Nevada
      • Reno, Nevada, United States, 89502
        • Renown Regional Medical Center
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
    • New Jersey
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey
      • Toms River, New Jersey, United States, 08755
        • Community Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • University of New Mexico Cancer Center
      • Albuquerque, New Mexico, United States, 87109
        • New Mexico Oncology Hematology Consultants
    • New York
      • Canandaigua, New York, United States, 14424
        • Sands Cancer Center
      • Dansville, New York, United States, 14437
        • Noyes Memorial Hospital/Myers Cancer Center
      • Oswego, New York, United States, 13126
        • Upstate Cancer Center at Oswego
      • Rochester, New York, United States, 14642
        • University of Rochester
      • Rochester, New York, United States, 14620
        • Highland 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
      • Syracuse, New York, United States, 13215
        • SUNY Upstate Medical Center-Community Campus
      • Verona, New York, United States, 13478
        • Upstate Cancer Center at Verona
      • Webster, New York, United States, 14580
        • Wilmot Cancer Institute at Webster
    • North Carolina
      • 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
      • Clemmons, North Carolina, United States, 27012
        • Wake Forest University at Clemmons
      • Concord, North Carolina, United States, 28025
        • Atrium Health Cabarrus/LCI-Concord
      • Gastonia, North Carolina, United States, 28054
        • CaroMont Regional Medical Center
      • Greenville, North Carolina, United States, 27834
        • East Carolina University
      • Huntersville, North Carolina, United States, 28078
        • Novant Health Cancer Institute - Huntersville
      • Huntersville, North Carolina, United States, 28078
        • Novant Health Presbyterian Medical Center Huntersville
      • Kernersville, North Carolina, United States, 27284
        • Novant Health Cancer Institute - Kernersville
      • 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
      • Mount Airy, North Carolina, United States, 27030
        • Novant Health Cancer Institute - Mount Airy
      • Pinehurst, North Carolina, United States, 28374
        • FirstHealth of the Carolinas-Moore Regional Hospital
      • Salisbury, North Carolina, United States, 28144
        • Novant Health Cancer Institute - Rowan
      • Statesville, North Carolina, United States, 28625
        • Novant Health Cancer Institute - Statesville
      • Statesville, North Carolina, United States, 28677
        • Wake Forest Baptist Health - Hematology Oncology - Statesville
      • Supply, North Carolina, United States, 28462
        • Novant Cancer Institute Radiation Oncology - Supply
      • Thomasville, North Carolina, United States, 27360
        • Novant Health Cancer Institute - Thomasville
      • Wilkesboro, North Carolina, United States, 28659
        • Novant Health Cancer Institute - Wilkesboro
      • Wilkesboro, North Carolina, United States, 28659
        • Wake Forest Baptist Health - Wilkes Medical Center
      • 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
      • Bismarck, North Dakota, United States, 58501
        • Sanford Bismarck Medical Center
      • Fargo, North Dakota, United States, 58122
        • Sanford Roger Maris Cancer Center
      • Fargo, North Dakota, United States, 58122
        • Sanford Broadway Medical Center
    • Ohio
      • Akron, Ohio, United States, 44304
        • Summa Health System - Akron Campus
      • Avon, Ohio, United States, 44011
        • UH Seidman Cancer Center at UH Avon Health Center
      • Barberton, Ohio, United States, 44203
        • Summa Health System - Barberton Campus
      • Chardon, Ohio, United States, 44024
        • Geauga Hospital
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Cancer Center-UC Medical Center
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
      • Cleveland, Ohio, United States, 44109
        • MetroHealth Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Cleveland, Ohio, United States, 44111
        • Cleveland Clinic Cancer Center/Fairview Hospital
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
      • Mansfield, Ohio, United States, 44906
        • Cleveland Clinic Cancer Center Mansfield
      • Mayfield Heights, Ohio, United States, 44124
        • Hillcrest Hospital Cancer Center
      • Medina, Ohio, United States, 44256
        • Summa Health Medina Medical Center
      • Mentor, Ohio, United States, 44060
        • UH Seidman Cancer Center at Lake Health Mentor Campus
      • Middleburg Heights, Ohio, United States, 44130
        • UH Seidman Cancer Center at Southwest General Hospital
      • Parma, Ohio, United States, 44129
        • University Hospitals Parma Medical Center
      • Perrysburg, Ohio, United States, 43551
        • Mercy Health Perrysburg Cancer Center
      • Ravenna, Ohio, United States, 44266
        • University Hospitals Portage Medical Center
      • Sandusky, Ohio, United States, 44870
        • North Coast Cancer Care
      • Strongsville, Ohio, United States, 44136
        • Cleveland Clinic Cancer Center Strongsville
      • Sylvania, Ohio, United States, 43560
        • ProMedica Flower Hospital
      • Toledo, Ohio, United States, 43608
        • Saint Vincent Mercy Medical Center
      • Toledo, Ohio, United States, 43623
        • Mercy Health - Saint Anne Hospital
      • Toledo, Ohio, United States, 43623
        • Mercy Health Sylvania Radiation Oncology Center
      • West Chester, Ohio, United States, 45069
        • University of Cincinnati Cancer Center-West Chester
      • Westlake, Ohio, United States, 44145
        • UH Seidman Cancer Center at Saint John Medical Center
      • Westlake, Ohio, United States, 44145
        • UHHS-Westlake Medical Center
      • Wooster, Ohio, United States, 44691
        • Cleveland Clinic Wooster Family Health and Surgery Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Oregon
      • Clackamas, Oregon, United States, 97015
        • Clackamas Radiation Oncology Center
      • Clackamas, Oregon, United States, 97015
        • Providence Cancer Institute Clackamas Clinic
      • Newberg, Oregon, United States, 97132
        • Providence Newberg Medical Center
      • Oregon City, Oregon, United States, 97045
        • Providence Willamette Falls Medical Center
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center
      • Portland, Oregon, United States, 97225
        • Providence Saint Vincent Medical Center
      • Portland, Oregon, United States, 97227
        • Kaiser Permanente Northwest
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Valley Hospital-Cedar Crest
      • Altoona, Pennsylvania, United States, 16601
        • UPMC Altoona
      • Beaver, Pennsylvania, United States, 15009
        • UPMC-Heritage Valley Health System Beaver
      • 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
      • East Norriton, Pennsylvania, United States, 19401
        • Fox Chase Cancer Center - East Norriton Hospital Outpatient Center
      • Ephrata, Pennsylvania, United States, 17522
        • Ephrata Cancer Center
      • Erie, Pennsylvania, United States, 16505
        • UPMC Hillman Cancer Center Erie
      • Farrell, Pennsylvania, United States, 16121
        • UPMC Cancer Center at UPMC Horizon
      • Furlong, Pennsylvania, United States, 18925
        • Fox Chase Cancer Center Buckingham
      • Gettysburg, Pennsylvania, United States, 17325
        • Adams Cancer Center
      • 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
      • Johnstown, Pennsylvania, United States, 15901
        • UPMC-Johnstown/John P. Murtha Regional Cancer Center
      • Lewisburg, Pennsylvania, United States, 17837
        • Geisinger Medical Oncology-Lewisburg
      • Lewistown, Pennsylvania, United States, 17044
        • Lewistown Hospital
      • McKeesport, Pennsylvania, United States, 15132
        • UPMC Cancer Center at UPMC McKeesport
      • 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, Pennsylvania, United States, 15108
        • UPMC Hillman Cancer Center in Coraopolis
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
      • Philadelphia, Pennsylvania, United States, 19114
        • Jefferson Torresdale Hospital
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University Hospital
      • Pittsburgh, Pennsylvania, United States, 15212
        • Allegheny General Hospital
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC-Magee Womens Hospital
      • 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
      • Seneca, Pennsylvania, United States, 16346
        • UPMC Cancer Center at UPMC Northwest
      • Uniontown, Pennsylvania, United States, 15401
        • UPMC Uniontown Hospital Radiation Oncology
      • Washington, Pennsylvania, United States, 15301
        • UPMC Washington Hospital Radiation Oncology
      • 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, 17403
        • WellSpan Health-York Hospital
      • York, Pennsylvania, United States, 17408
        • UPMC Memorial
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Gaffney, South Carolina, United States, 29341
        • Gibbs Cancer Center-Gaffney
      • Georgetown, South Carolina, United States, 29440
        • Tidelands Georgetown Memorial Hospital
      • Greenville, South Carolina, United States, 29605
        • Prisma Health Cancer Institute - Faris
      • Greenville, South Carolina, United States, 29607
        • Saint Francis Cancer Center
      • Greenville, South Carolina, United States, 29615
        • Prisma Health Cancer Institute - Eastside
      • Greenville, South Carolina, United States, 29601
        • Saint Francis Hospital
      • Greer, South Carolina, United States, 29650
        • Prisma Health Cancer Institute - Greer
      • Greer, South Carolina, United States, 29651
        • Gibbs Cancer Center-Pelham
      • Rock Hill, South Carolina, United States, 29732
        • Levine Cancer Institute-Rock Hill
      • Rock Hill, South Carolina, United States, 29730
        • Rock Hill Radiation Therapy Center
      • Seneca, South Carolina, United States, 29672
        • Prisma Health Cancer Institute - Seneca
      • Spartanburg, South Carolina, United States, 29303
        • Spartanburg Medical Center
      • Union, South Carolina, United States, 29379
        • MGC Hematology Oncology-Union
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Avera Cancer Institute
      • Sioux Falls, South Dakota, United States, 57117-5134
        • Sanford USD Medical Center - Sioux Falls
      • Sioux Falls, South Dakota, United States, 57104
        • Sanford Cancer Center Oncology Clinic
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • The West Clinic - Wolf River
      • Knoxville, Tennessee, United States, 37920
        • University of Tennessee - Knoxville
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University/Ingram Cancer Center
    • Texas
      • Amarillo, Texas, United States, 79106
        • The Don and Sybil Harrington Cancer Center
    • 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
      • Saint George, Utah, United States, 84770
        • Saint George Regional Medical Center
      • 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
    • Vermont
      • Saint Johnsbury, Vermont, United States, 05819
        • Norris Cotton Cancer Center-North
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Inova Schar Cancer Institute
      • Fairfax, Virginia, United States, 22033
        • Inova Fair Oaks Hospital
      • Portsmouth, Virginia, United States, 23708-2197
        • Naval Medical Center - Portsmouth
      • Richmond, Virginia, United States, 23235
        • VCU Massey Cancer Center at Stony Point
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University/Massey Cancer Center
    • Washington
      • Renton, Washington, United States, 98055
        • Valley Medical Center
      • Seattle, Washington, United States, 98107
        • Swedish Medical Center-Ballard Campus
      • Seattle, Washington, United States, 98122
        • Swedish Medical Center-First Hill
      • Walla Walla, Washington, United States, 99362
        • Providence Saint Mary Regional Cancer Center
    • Wisconsin
      • Antigo, Wisconsin, United States, 54409
        • Langlade Hospital and Cancer Center
      • Appleton, Wisconsin, United States, 54915
        • Ascension Saint Elizabeth Hospital
      • Ashland, Wisconsin, United States, 54806
        • Duluth Clinic Ashland
      • 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
        • HSHS Sacred Heart Hospital
      • Franklin, Wisconsin, United States, 53132
        • Ascension Saint Francis - Reiman Cancer Center
      • Franklin, Wisconsin, United States, 53132
        • Ascension Southeast Wisconsin Hospital - Franklin
      • 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
      • Hayward, Wisconsin, United States, 54843
        • Essentia Health-Hayward Clinic
      • Johnson Creek, Wisconsin, United States, 53038
        • UW Cancer Center Johnson Creek
      • Kenosha, Wisconsin, United States, 53142
        • Aurora Cancer Care-Kenosha South
      • La Crosse, Wisconsin, United States, 54601
        • Gundersen Lutheran Medical Center
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Carbone Cancer Center
      • Marinette, Wisconsin, United States, 54143
        • Aurora Bay Area Medical Group-Marinette
      • 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, 53210
        • Ascension Southeast Wisconsin Hospital - Saint Joseph Campus
      • Milwaukee, Wisconsin, United States, 53211
        • Ascension Columbia Saint Mary's Hospital - Milwaukee
      • Milwaukee, Wisconsin, United States, 53215
        • Ascension Saint Francis Hospital
      • 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
        • Ascension Saint Mary's Hospital
      • Sheboygan, Wisconsin, United States, 53081
        • Vince Lombardi Cancer Clinic-Sheboygan
      • Spooner, Wisconsin, United States, 54801
        • Essentia Health-Spooner Clinic
      • Stevens Point, Wisconsin, United States, 54481
        • Ascension Saint Michael's Hospital
      • Summit, Wisconsin, United States, 53066
        • Aurora Medical Center in Summit
      • Superior, Wisconsin, United States, 54880
        • Essentia Health Saint Mary's Hospital - Superior
      • 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
      • Wisconsin Rapids, Wisconsin, United States, 54494
        • Aspirus Cancer Care - Wisconsin Rapids

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma and basaloid squamous cell carcinoma but not neuroendocrine phenotype) of the oropharynx (tonsil, base of tongue, soft palate, or oropharyngeal walls); cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx. Clinical evidence should be documented, may consist of palpation, imaging, or endoscopic evaluation, and should be sufficient to estimate the size of the primary (for T stage)
  • Patients must have clinically or radiographically evident measurable disease at the primary site or at nodal stations. Simple tonsillectomy or local excision of the primary without removal of nodal disease is permitted, as is excision removing gross nodal disease but with intact primary site. Limited neck dissections retrieving =< 4 nodes are permitted and considered as non-therapeutic nodal excisions

  • P16-positive based on local site immunohistochemical tissue staining (defined as greater than 70% strong diffuse nuclear or nuclear and cytoplasmic staining of tumor cells). Fine needle aspiration (FNA) biopsy specimens may be used as the sole diagnostic tissue. Centers are encouraged to contact the pathology chair for clarification

    • Note: Institutions must screen patients, whose tumors must be p16-positive by immunohistochemistry (IHC) in order to be eligible for the trial using a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. A rigorous laboratory accreditation process similar to the United States (U.S.) CLIA certification, such as the provincial accreditation status offered by the Ontario Laboratory Accreditation (OLA) Program in Canada, the College of American Pathologists (CAP), or an equivalent accreditation in other countries, is acceptable. The p16-positive results must be reported on the pathology report being submitted
    • Note: If p16 result is equivocal, positive HPV deoxyribonucleic acid (DNA) test of tumor specimen is acceptable and fulfills the eligibility criteria

  • Clinical stage T1-2, N1, M0 (American Joint Committee on Cancer [AJCC], 8th edition [ed.]) or T3, N0-N1, M0 (AJCC, 8th ed.) including no distant metastases based on the following diagnostic workup:

    • General history and physical examination within 56 days prior to registration;
    • Exam with laryngopharyngoscopy (mirror or in office direct procedure acceptable) within 70 days prior to registration;

    • One of the following imaging studies is required within 56 days prior to registration:

      • FDG-PET/CT of the neck and chest (with or without contrast); FDG-PET/CT scan is strongly preferred and highly recommended to be used for eligibility OR
      • Chest CT (with or without contrast)

    • One of the following imaging studies is required within 28 days prior to registration:

      • A diagnostic CT scan of neck (with contrast and of diagnostic quality) OR
      • An magnetic resonance imaging (MRI) of the neck (with contrast and of diagnostic quality)
      • Note: A diagnostic quality CT or MRI with contrast or FDG-PET/CT scan of neck performed for the purposes of radiation planning may serve as both staging and planning tools

  • Patients must provide their personal smoking history prior to registration. The lifetime cumulative history cannot exceed 10 pack-years. The following formula is used to calculate the pack-years during the periods of smoking in the patient's life; the cumulative total of the number of pack-years during each period of active smoking is the lifetime cumulative history

    • Number of pack-years = [Frequency of smoking (number of cigarettes per day) x duration of cigarette smoking (years)] / 20
    • Note: Twenty cigarettes is considered equivalent to one pack. The effect of non-cigarette tobacco products on the survival of patients with p16-positive oropharyngeal cancers is undefined. While there are reportedly increased risks of head and neck cancer associated with sustained heavy cigar and pipe use (Wyss 2013), such sustained use of non-cigarette products is unusual and does not appear to convey added risk with synchronous cigarette smoking. Cigar and pipe tobacco consumption is therefore not included in calculating the lifetime pack-years. Marijuana consumption is likewise not considered in this calculation. There is no clear scientific evidence regarding the role of chewing tobacco-containing products in this disease, although this is possibly more concerning given the proximity of the oral cavity and oropharynx. In any case, investigators are discouraged from enrolling patients with a history of very sustained use (such as several years or more) of non-cigarette tobacco products alone
  • Zubrod performance status of 0-1 within 14 days prior to registration
  • Age >= 18
  • Absolute neutrophil count >= 1,500/mcL (within 14 days prior to registration)
  • Platelets >= 100,000/mcL (within 14 days prior to registration)
  • Hemoglobin >= 8.0 g/dL (within 14 days prior to registration) (Note: use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dL is acceptable)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 14 days prior to registration)
  • Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional ULN (within 14 days prior to registration)
  • Serum creatinine =< 1.5 x ULN OR creatinine clearance (CrCl) >= 50 mL/min (if using the Cockcroft-Gault formula) (within 14 days prior to registration)
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

    • Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)

  • 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 for the hepatitis, they are eligible if they have an undetectable HCV viral load.

    • Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy

  • For women of childbearing potential (WOCBP), negative serum or urine pregnancy test within 24 hours prior to registration

    • Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
  • Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must be willing to use an adequate method of contraception during and after treatment
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
  • Only English, Spanish, or French speaking patients are eligible to participate as these are the only languages for which the mandatory dysphagia-related patient reported instrument (MDADI) is available

Exclusion Criteria:

  • Clinical stages T0; T4; T1-2, N0; or any N2 (AJCC, 8th ed)
  • Recurrent disease
  • Definitive clinical or radiologic evidence of metastatic disease or adenopathy below the clavicles
  • Cancers considered to be from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16-positive, or histologies of adenosquamous, verrucous, or spindle cell carcinomas
  • Carcinoma of the neck of unknown primary site origin (T0 is ineligible, even if p16-positive)
  • Radiographically matted nodes, defined as 3 abutting nodes with loss of the intervening fat plane
  • Supraclavicular nodes, defined as nodes centered below the level of the cricoid cartilage
  • Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. In other words, to participate in this protocol, the patient must have clinically or radiographically evident gross disease for which disease response can be assessed
  • Patients with simultaneous primary cancers or separate bilateral primary tumor sites are excluded with the exception of patients with bilateral tonsil cancers
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (of note, the exclusion applies only for invasive cancers such that carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
  • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
  • History of severe hypersensitivity reaction to any monoclonal antibody.

  • Severe, active co-morbidity defined as follows:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    • Transmural myocardial infarction within the last 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
    • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition with immune compromise greater than that noted; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients
    • Condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
    • Patients with active autoimmune disease requiring systemic treatment (i.e. disease modifying agents, corticosteroids, or immunosuppressive drugs) should be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), rheumatoid arthritis, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease
    • Note: Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
  • Patients who are pregnant, nursing, or expecting to conceive or father children
  • Prior allergic reaction to cisplatin

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm I (IMRT, IGRT, cisplatin)
Patients undergo IMRT or IGRT over 6 fractions per week and receive cisplatin IV over 30-60 minutes on days 1 and 22. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients receive FDG and undergo PET/CT or CT during screening and during follow up, and undergo MRI during follow up. Patients may also undergo tissue biopsy and 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: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Drug: Cisplatin
Given IV
Other Names:
  • CDDP
  • Cis-diamminedichloridoplatinum
  • Cismaplat
  • Cisplatinum
  • Neoplatin
  • Platinol
  • Abiplatin
  • Blastolem
  • Briplatin
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cisplatina
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Procedure: Computed Tomography
Undergo CT
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: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy
  • Intensity modulated radiation therapy (procedure)
Procedure: Positron Emission Tomography
Undergo PET
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT
  • Positron emission tomography (procedure)
Radiation: Image Guided Radiation Therapy
Undergo IGRT
Other Names:
  • IGRT
  • image-guided radiation therapy
  • Image-Guided Radiotherapy
Procedure: Biopsy
Undergo tissue biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
Other: Fludeoxyglucose F-18
Receive FDG
Other Names:
  • 18FDG
  • FDG
  • fludeoxyglucose F 18
  • Fludeoxyglucose (18F)
  • Fludeoxyglucose F18
  • Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
  • Fluorodeoxyglucose F18
Experimental: Arm II (IMRT, IGRT, cisplatin)
Patients undergo reduced dose IMRT or IGRT QD over 5 fractions per week and receive cisplatin IV over 30-60 minutes on days 1 and 22. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients receive FDG and undergo PET/CT or CT during screening and during follow up, and undergo MRI during follow up. Patients may also undergo tissue biopsy and 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: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Drug: Cisplatin
Given IV
Other Names:
  • CDDP
  • Cis-diamminedichloridoplatinum
  • Cismaplat
  • Cisplatinum
  • Neoplatin
  • Platinol
  • Abiplatin
  • Blastolem
  • Briplatin
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cisplatina
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Procedure: Computed Tomography
Undergo CT
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: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy
  • Intensity modulated radiation therapy (procedure)
Procedure: Positron Emission Tomography
Undergo PET
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT
  • Positron emission tomography (procedure)
Radiation: Image Guided Radiation Therapy
Undergo IGRT
Other Names:
  • IGRT
  • image-guided radiation therapy
  • Image-Guided Radiotherapy
Procedure: Biopsy
Undergo tissue biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
Other: Fludeoxyglucose F-18
Receive FDG
Other Names:
  • 18FDG
  • FDG
  • fludeoxyglucose F 18
  • Fludeoxyglucose (18F)
  • Fludeoxyglucose F18
  • Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
  • Fluorodeoxyglucose F18
Experimental: Arm III (IMRT, IGRT, nivolumab)
Beginning 1 week prior to radiation, patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks (14 days) for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo reduced dose IMRT or IGRT over 6 fractions per week for 5 weeks in the absence of disease progression or unacceptable toxicity. Patients receive FDG and undergo PET/CT or CT during screening and during follow up, and undergo MRI during follow up. Patients may also undergo tissue biopsy and blood sample collection throughout the study.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • CMAB819
  • Nivolumab Biosimilar CMAB819
  • ABP 206
  • Nivolumab Biosimilar ABP 206
  • BCD-263
  • Nivolumab Biosimilar BCD-263
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Procedure: Computed Tomography
Undergo CT
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: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy
  • Intensity modulated radiation therapy (procedure)
Procedure: Positron Emission Tomography
Undergo PET
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT
  • Positron emission tomography (procedure)
Radiation: Image Guided Radiation Therapy
Undergo IGRT
Other Names:
  • IGRT
  • image-guided radiation therapy
  • Image-Guided Radiotherapy
Procedure: Biopsy
Undergo tissue biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
Other: Fludeoxyglucose F-18
Receive FDG
Other Names:
  • 18FDG
  • FDG
  • fludeoxyglucose F 18
  • Fludeoxyglucose (18F)
  • Fludeoxyglucose F18
  • Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
  • Fluorodeoxyglucose F18

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS) (Phase II)
Time Frame: Up to 6 years
Will be estimated for all treatment arms using the Kaplan-Meier method (1958). The primary phase IIR endpoint will be tested using a confidence interval (CI) approach.
Up to 6 years
PFS (Phase III)
Time Frame: Up to 6 years
Will be estimated for all treatment arms using the Kaplan-Meier method (1958). The co-primary phase III endpoint will be tested using a confidence interval (CI) approach.
Up to 6 years
Quality of life
Time Frame: Baseline up to 6 years
Measured by the MD Anderson Dysphagia Inventory (MDADI) global quality of life (QOL) score. Will be compared between arms using a two-sample independent t-test at a one-sided significance level of 0.05 for each experimental arm comparison. MDADI global score and change from baseline will be summarized using mean and standard deviation at each time point for each arm.
Baseline up to 6 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Locoregional failure
Time Frame: From the time of randomization to the date of failure, date of precluding event, or last known follow-up date, assessed up to 6 years
The cumulative incidence estimator will be used to estimate time to event distributions for locoregional failure between arm differences tested using cause-specific log-rank test.
From the time of randomization to the date of failure, date of precluding event, or last known follow-up date, assessed up to 6 years
Distant failure
Time Frame: Up to 6 years
Up to 6 years
Overall survival
Time Frame: 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 6 years
Will be estimated using the Kaplan-Meier method and treatment arms compared using the 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 6 years
Incidence of adverse events
Time Frame: Up to 6 years
Measured by the Common Terminology Criteria for Adverse Events (CTCAE). Adverse events (AEs) will be graded using CTCAE version (v)5.0. Counts of all AEs by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm. The number of patients with at least 1 grade 3 or higher AE will be compared between the treatment arms. A comparison between treatment arms of grade 3 and higher AEs related to treatment will also be tested. A comparison of grade 3 and higher events will be compared between treatment arms. All comparisons will be tested using a Chi-Square test, or Fisher's exact test if cell frequencies are < 5, with a significance level of 0.05.
Up to 6 years
Hearing
Time Frame: Baseline up to 24 months from end of radiation therapy (RT)
Measured as Hearing Handicap Inventory for Adults-Screening (HHIA-S).
Baseline up to 24 months from end of radiation therapy (RT)
Quality of life
Time Frame: Baseline up to 24 months from end of RT
Measured by the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire (QLQ)30.
Baseline up to 24 months from end of RT
Fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) locoregional control
Time Frame: Up to 6 years
Will be associated with PFS.
Up to 6 years
Negative predictive value of post-RT FDG-PET/CT for locoregional control
Time Frame: At 1 and 2 years
The negative predictive value of FDG-PET/CT for locoregional control will be estimated using binomial proportions and confidence intervals based on normal approximation.
At 1 and 2 years
Negative predictive value of post-RT FDG-PET/CT for PFS
Time Frame: At 1 and 2 years
The negative predictive value of FDG-PET/CT PFS will be estimated using binomial proportions and confidence intervals based on normal approximation.
At 1 and 2 years
Incidence of adverse events
Time Frame: Up to 6 years
Measured using Patient-Reported Outcomes (PRO)-CTCAE. For each symptom, counts and frequencies will be provided for the worst score experienced by the patient by treatment arm. The proportion of patients with scores >= 1 and >= 3 will be compared between groups using a Chi-square test, or Fisher's exact test if cell frequencies are < 5, using a significance level of 0.05. Analysis of changes in patient reported outcomes over time will analyzed by fitting generalized estimating equations (GEE) models using a logit link (dichotomizing the symptom scores as 0 vs. > 1 and 0-2 vs. 3-4) with time of assessment, treatment arm, and treatment-by-time interaction terms in the model.
Up to 6 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of life
Time Frame: Baseline up to 24 months from end of RT
Measured by EuroQol-5 Dimensional- 5 Level (EQ-5D-5L).
Baseline up to 24 months from end of RT
Swallowing physiology
Time Frame: Up to 6 years
Measured by a Modified Barium Swallow (MBS) test. The proportion of aspiration for each arm will be estimated assuming a binomial distribution and between arm comparison will be performed using a Fisher's exact test.
Up to 6 years
Locoregional control for patients with post-RT FDG-PET/CT
Time Frame: At 12-14 weeks post-RT
Locoregional control rates will be compared between negative and positive/undetermined patients. Cox proportional hazards models will be used to determine whether there are differences between these two groups, while adjusting for treatment arm and other covariates (cause-specific Cox models for locoregional failure).
At 12-14 weeks post-RT
PFS for patients with post-RT FDG-PET/CT
Time Frame: At 12-14 weeks post-RT
PFS rates will be compared between negative and positive/undetermined patients. Cox proportional hazards models will be used to determine whether there are differences between these two groups, while adjusting for treatment arm and other covariates (cause-specific Cox models for locoregional failure).
At 12-14 weeks post-RT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Collaborators

NRG Oncology

Investigators

  • Principal Investigator: Sue S Yom, NRG Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 9, 2019

Primary Completion (Estimated)

February 28, 2025

Study Completion (Estimated)

February 28, 2025

Study Registration Dates

First Submitted

May 15, 2019

First Submitted That Met QC Criteria

May 15, 2019

First Posted (Actual)

May 16, 2019

Study Record Updates

Last Update Posted (Actual)

April 24, 2024

Last Update Submitted That Met QC Criteria

April 23, 2024

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2019-03015 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180868 (U.S. NIH Grant/Contract)
  • NRG-HN005 (Other Identifier: CTEP)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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