Veliparib, Pembrolizumab, and Combination Chemotherapy in Treating Patient With Locally Advanced Rectal Cancer

September 21, 2023 updated by: National Cancer Institute (NCI)

A Phase II Clinical Trial Platform of Sensitization Utilizing Total Neoadjuvant Therapy (TNT) in Rectal Cancer

This randomized phase II trial studies how well veliparib or pembrolizumab work with combination chemotherapy and radiation therapy in treating patients with rectal cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced). Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as modified (m)FOLFOX6 regimen, 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. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving veliparib or pembrolizumab with combination chemotherapy and radiation therapy may kill more tumor cells, make the tumor smaller, and reduce the amount of normal tissue that needs to be removed.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To demonstrate an absolute improvement in neoadjuvant rectal cancer (NAR) score for the experimental regimen as compared to concurrently randomized control patients.

SECONDARY OBJECTIVES:

I. To compare overall survival (OS). II. To compare disease-free survival (DFS). III. To compare the rate of pathologic complete response (pCR) (nodes and tumor).

IV. To compare the rate of sphincter preservation.

TERTIARY OBJECTIVES:

I. To compare the proportion of patients who have a tumor resection overall, conditional on beginning induction chemotherapy, and conditional on beginning chemoradiotherapy.

II. To compare time from initiation of chemoradiotherapy to surgery in the subset of patients with tumor resection.

EXPLORATORY OBJECTIVES:

I. To estimate the rate of disease progression during chemotherapy (prior to chemoradiation).

II. To compare the rate of clinical complete response rate (cCR). III. To compare the rate of negative circumferential margin. IV. To compare the rate of completion of all cycles of neoadjuvant chemotherapy.

V. To compare the rate of completion of full course of chemoradiation. VI. To compare the toxicity and safety between interventions. VII. To explore the correlative molecular predictors of response and distant failure.

VIII. To explore the relationship between radiographic findings and pathologic outcomes.

OUTLINE: Patients are sequentially randomized to treatment arms, initially ARM I or ARM II and then later either ARM I or ARM III.

ARM I: Patients receive mFOLFOX6 regimen consisting of oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. 3-4 weeks after last does of mFOLFOX6 patient undergo radiation therapy (RT) and receive capecitabine orally (PO) twice daily (BID) Monday-Friday for 5 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive mFOLFOX6 regimen consisting of oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. 3-4 weeks after last does of mFOLFOX6 patient undergo RT and receive capecitabine PO BID and veliparib PO BID Monday-Friday for 5 weeks in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive mFOLFOX6 regimen consisting of oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. 3-4 weeks after last does of mFOLFOX6 patient undergo RT and receive capecitabine PO BID Monday-Friday for 5 weeks. They also receive pembrolizumab IV over 30 minutes every 3 weeks beginning on day 1 of RT for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and every 6 months for up to 3 years.

Study Type

Interventional

Enrollment (Actual)

363

Phase

Phase 2

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

Puerto Rico
- - Bayamon, Puerto Rico, 00959-5060
    - Cancer Center-Metro Medical Center Bayamon
  - Manati, Puerto Rico, 00674
    - Doctors Cancer Center
  - San Juan, Puerto Rico, 00917
    - San Juan Community Oncology Group
  - San Juan, Puerto Rico, 00927
    - Centro Comprensivo de Cancer de UPR
  - San Juan, Puerto Rico, 00936
    - San Juan City Hospital
United States
- Alabama
  - Birmingham, Alabama, United States, 35233
    - University of Alabama at Birmingham Cancer Center
  - Mobile, Alabama, United States, 36688
    - University of South Alabama Mitchell Cancer Institute
  - Mobile, Alabama, United States, 36607
    - Southern Cancer Center PC-Mobile
  - Mobile, Alabama, United States, 36608
    - Southern Cancer Center PC-Providence
  - Mobile, Alabama, United States, 36608
    - Southern Cancer Center PC-Springhill
- Alaska
  - Fairbanks, Alaska, United States, 99701
    - Fairbanks Memorial Hospital
- Arizona
  - Gilbert, Arizona, United States, 85234
    - Banner MD Anderson Cancer Center
  - Scottsdale, Arizona, United States, 85259
    - Mayo Clinic in Arizona
  - Tucson, Arizona, United States, 85704
    - University of Arizona Cancer Center-Orange Grove Campus
  - Tucson, Arizona, United States, 85719
    - Banner University Medical Center - Tucson
  - Tucson, Arizona, United States, 85719
    - University of Arizona Cancer Center-North Campus
- Arkansas
  - Fort Smith, Arkansas, United States, 72903
    - Mercy Hospital Fort Smith
  - Hot Springs, Arkansas, United States, 71913
    - CHI Saint Vincent Cancer Center Hot Springs
  - Jonesboro, Arkansas, United States, 72401
    - NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
  - Little Rock, Arkansas, United States, 72205
    - University of Arkansas for Medical Sciences
- California
  - Anaheim, California, United States, 92806
    - Kaiser Permanente-Anaheim
  - Antioch, California, United States, 94531
    - Kaiser Permanente-Deer Valley Medical Center
  - Arroyo Grande, California, United States, 93420
    - PCR Oncology
  - 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
  - Burlingame, California, United States, 94010
    - Mills-Peninsula Medical Center
  - Cameron Park, California, United States, 95682
    - Sutter Cancer Centers Radiation Oncology Services-Cameron Park
  - Castro Valley, California, United States, 94546
    - Eden Hospital Medical Center
  - Chico, California, United States, 95926
    - Enloe Medical Center
  - Corona, California, United States, 92879
    - City of Hope Corona
  - Duarte, California, United States, 91010
    - City of Hope Comprehensive Cancer Center
  - Dublin, California, United States, 94568
    - Kaiser Permanente Dublin
  - Fremont, California, United States, 94538
    - Kaiser Permanente-Fremont
  - Fresno, California, United States, 93720
    - Kaiser Permanente-Fresno
  - Fresno, California, United States, 93720
    - Fresno Cancer Center
  - 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, 90033
    - Los Angeles County-USC Medical Center
  - Los Angeles, California, United States, 90027
    - Kaiser Permanente Los Angeles Medical Center
  - Los Angeles, California, United States, 90048
    - Cedars Sinai 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
  - Mountain View, California, United States, 94040
    - Palo Alto Medical Foundation-Camino Division
  - Novato, California, United States, 94945
    - Sutter Cancer Research Consortium
  - Oakland, California, United States, 94611
    - Kaiser Permanente-Oakland
  - Oakland, California, United States, 94611
    - Kaiser Permanente Oakland-Broadway
  - Orange, California, United States, 92868
    - UC Irvine Health/Chao Family Comprehensive Cancer Center
  - 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-Redwood City
  - Richmond, California, United States, 94801
    - Kaiser Permanente-Richmond
  - Riverside, California, United States, 92505
    - Kaiser Permanente-Riverside
  - 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
  - Sacramento, California, United States, 95825
    - Kaiser Permanente - Sacramento
  - San Diego, California, United States, 92120
    - Kaiser Permanente-San Diego Zion
  - San Francisco, California, United States, 94115
    - Kaiser Permanente-San Francisco
  - San Francisco, California, United States, 94115
    - California Pacific Medical Center-Pacific Campus
  - San Jose, California, United States, 95119
    - Kaiser Permanente-Santa Teresa-San Jose
  - San Leandro, California, United States, 94577
    - Kaiser Permanente San Leandro
  - San Marcos, California, United States, 92078
    - Kaiser Permanente-San Marcos
  - San Rafael, California, United States, 94903
    - Kaiser San Rafael-Gallinas
  - San Rafael, California, United States, 94903
    - Kaiser Permanente-San Rafael
  - 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
  - Truckee, California, United States, 96161
    - Gene Upshaw Memorial Tahoe Forest Cancer Center
  - Upland, California, United States, 91786
    - City of Hope Upland
  - Vacaville, California, United States, 95688
    - Kaiser Permanente Medical Center-Vacaville
  - Vacaville, California, United States, 95687
    - Sutter Cancer Centers Radiation Oncology Services-Vacaville
  - Vallejo, California, United States, 94589
    - Kaiser Permanente-Vallejo
  - Vallejo, California, United States, 94589
    - Sutter Solano Medical Center/Cancer Center
  - Walnut Creek, California, United States, 94596
    - Kaiser Permanente-Walnut Creek
  - Whittier, California, United States, 90602
    - Presbyterian Intercommunity Hospital
- Colorado
  - Aurora, Colorado, United States, 80012
    - Rocky Mountain Cancer Centers-Aurora
  - Aurora, Colorado, United States, 80045
    - UCHealth University of Colorado Hospital
  - Boulder, Colorado, United States, 80301
    - Boulder Community Hospital
  - Boulder, Colorado, United States, 80304
    - Rocky Mountain Cancer Centers-Boulder
  - Colorado Springs, Colorado, United States, 80907
    - Penrose-Saint Francis Healthcare
  - Colorado Springs, Colorado, United States, 80909
    - UCHealth Memorial Hospital Central
  - Colorado Springs, Colorado, United States, 80907
    - Rocky Mountain Cancer Centers-Penrose
  - Denver, Colorado, United States, 80210
    - Porter Adventist Hospital
  - Denver, Colorado, United States, 80218
    - Presbyterian - Saint Lukes Medical Center - Health One
  - Denver, Colorado, United States, 80218
    - SCL Health Saint Joseph Hospital
  - Englewood, Colorado, United States, 80113
    - Swedish Medical Center
  - Fort Collins, Colorado, United States, 80524
    - Poudre Valley Hospital
  - Grand Junction, Colorado, United States, 81501
    - Saint Mary's Hospital and Regional Medical Center
  - Greeley, Colorado, United States, 80631
    - North Colorado Medical Center
  - Lakewood, Colorado, United States, 80228
    - Saint Anthony Hospital
  - Littleton, Colorado, United States, 80120
    - Rocky Mountain Cancer Centers-Littleton
  - Littleton, Colorado, United States, 80122
    - Littleton Adventist Hospital
  - Longmont, Colorado, United States, 80501
    - Longmont United Hospital
  - Loveland, Colorado, United States, 80539
    - McKee Medical Center
  - Pueblo, Colorado, United States, 81004
    - Saint Mary Corwin Medical Center
  - Thornton, Colorado, United States, 80260
    - Rocky Mountain Cancer Centers-Thornton
  - Wheat Ridge, Colorado, United States, 80033
    - SCL Health Lutheran Medical Center
- Connecticut
  - Guilford, Connecticut, United States, 06437
    - Smilow Cancer Hospital Care Center - Guilford
  - 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
  - New Haven, Connecticut, United States, 06510
    - Smilow Cancer Center/Yale-New Haven Hospital
  - North Haven, Connecticut, United States, 06473
    - Yale-New Haven Hospital North Haven Medical Center
  - Norwich, Connecticut, United States, 06360
    - William Backus Hospital
  - Trumbull, Connecticut, United States, 06611
    - Smilow Cancer Hospital Care Center-Trumbull
  - Waterford, Connecticut, United States, 06385
    - Smilow Cancer Hospital Care Center - Waterford
- Delaware
  - Lewes, Delaware, United States, 19958
    - Beebe Medical Center
  - 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
  - Rehoboth Beach, Delaware, United States, 19971
    - Beebe Health Campus
  - Seaford, Delaware, United States, 19973
    - TidalHealth Nanticoke / Allen Cancer Center
- Florida
  - Gainesville, Florida, United States, 32610
    - University of Florida Health Science Center - Gainesville
  - Jacksonville, Florida, United States, 32224-9980
    - Mayo Clinic in Florida
  - Orlando, Florida, United States, 32806
    - Orlando Health Cancer Institute
- 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
  - Gainesville, Georgia, United States, 30501
    - Northeast Georgia Medical Center-Gainesville
  - Savannah, Georgia, United States, 31405
    - Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
  - Savannah, Georgia, United States, 31404
    - Memorial Health University Medical Center
- Hawaii
  - 'Aiea, Hawaii, United States, 96701
    - Pali Momi Medical Center
  - 'Aiea, Hawaii, United States, 96701
    - Queen's Cancer Center - Pearlridge
  - 'Aiea, Hawaii, United States, 96701
    - The Cancer Center of Hawaii-Pali Momi
  - 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
    - 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, 96813
    - Island Urology
  - 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
  - Caldwell, Idaho, United States, 83605
    - Saint Alphonsus Cancer Care Center-Caldwell
  - Meridian, Idaho, United States, 83642
    - Idaho Urologic Institute-Meridian
  - Post Falls, Idaho, United States, 83854
    - Kootenai Clinic Cancer Services - Post Falls
- Illinois
  - Arlington Heights, Illinois, United States, 60005
    - Northwest Community Hospital
  - Aurora, Illinois, United States, 60504
    - Rush - Copley Medical Center
  - Bloomington, Illinois, United States, 61704
    - Illinois CancerCare-Bloomington
  - Carbondale, Illinois, United States, 62902
    - Memorial Hospital of Carbondale
  - Carterville, Illinois, United States, 62918
    - SIH Cancer Institute
  - Centralia, Illinois, United States, 62801
    - Centralia Oncology Clinic
  - Chicago, Illinois, United States, 60611
    - Northwestern University
  - Chicago, Illinois, United States, 60637
    - University of Chicago Comprehensive Cancer Center
  - Chicago, Illinois, United States, 60657
    - Advocate Illinois Masonic Medical Center
  - Danville, Illinois, United States, 61832
    - Carle at The Riverfront
  - Decatur, Illinois, United States, 62526
    - Decatur Memorial Hospital
  - Decatur, Illinois, United States, 62526
    - Cancer Care Specialists of Illinois - Decatur
  - Effingham, Illinois, United States, 62401
    - Crossroads Cancer Center
  - Effingham, Illinois, United States, 62401
    - Carle Physician Group-Effingham
  - Galesburg, Illinois, United States, 61401
    - Western Illinois Cancer Treatment Center
  - Geneva, Illinois, United States, 60134
    - Northwestern Medicine Cancer Center Delnor
  - Harvey, Illinois, United States, 60426
    - Ingalls Memorial Hospital
  - Lake Forest, Illinois, United States, 60045
    - Northwestern Medicine Lake Forest Hospital
  - Mattoon, Illinois, United States, 61938
    - Carle Physician Group-Mattoon/Charleston
  - Maywood, Illinois, United States, 60153
    - Loyola University Medical Center
  - Mount Vernon, Illinois, United States, 62864
    - Good Samaritan Regional Health Center
  - New Lenox, Illinois, United States, 60451
    - UC Comprehensive Cancer Center at Silver Cross
  - O'Fallon, Illinois, United States, 62269
    - Cancer Care Center of O'Fallon
  - Ottawa, Illinois, United States, 61350
    - Illinois CancerCare-Ottawa Clinic
  - Pekin, Illinois, United States, 61554
    - OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
  - 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
  - Peoria, Illinois, United States, 61615
    - OSF Saint Francis Radiation Oncology at Peoria Cancer Center
  - Peru, Illinois, United States, 61354
    - Illinois CancerCare-Peru
  - Peru, Illinois, United States, 61354
    - Valley Radiation Oncology
  - Princeton, Illinois, United States, 61356
    - Illinois CancerCare-Princeton
  - Rockford, Illinois, United States, 61114
    - SwedishAmerican Regional Cancer Center/ACT
  - Silvis, Illinois, United States, 61282
    - Genesis Cancer Center - Silvis
  - 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
  - Springfield, Illinois, United States, 62702
    - Central Illinois Hematology Oncology Center
  - Swansea, Illinois, United States, 62226
    - Southwest Illinois Health Services LLP
  - Urbana, Illinois, United States, 61801
    - Carle Cancer Center
  - Warrenville, Illinois, United States, 60555
    - Northwestern Medicine Cancer Center Warrenville
- Indiana
  - Evansville, Indiana, United States, 47713
    - Deaconess Clinic Downtown
  - Fort Wayne, Indiana, United States, 46805
    - Parkview Hospital Randallia
  - Fort Wayne, Indiana, United States, 46845
    - Parkview Regional Medical Center
  - Goshen, Indiana, United States, 46526
    - Goshen Center for Cancer Care
  - Indianapolis, Indiana, United States, 46237
    - Franciscan Health Indianapolis
  - Michigan City, Indiana, United States, 46360
    - Woodland Cancer Care Center
  - Mishawaka, Indiana, United States, 46545
    - Memorial Regional Cancer Center Day Road
  - Mooresville, Indiana, United States, 46158
    - Franciscan Health Mooresville
  - Newburgh, Indiana, United States, 47630
    - Chancellor Center for Oncology
  - Richmond, Indiana, United States, 47374
    - Reid Health
  - South Bend, Indiana, United States, 46601
    - Memorial Hospital of South Bend
- Iowa
  - Ames, Iowa, United States, 50010
    - Mary Greeley Medical Center
  - Ames, Iowa, United States, 50010
    - McFarland Clinic - Ames
  - Cedar Rapids, Iowa, United States, 52403
    - Mercy Hospital
  - Cedar Rapids, Iowa, United States, 52403
    - Oncology Associates at Mercy Medical Center
  - Clive, Iowa, United States, 50325
    - Mercy Cancer Center-West Lakes
  - Clive, Iowa, United States, 50325
    - Medical Oncology and Hematology Associates-West Des Moines
  - Davenport, Iowa, United States, 52803
    - Genesis Medical Center - East Campus
  - Davenport, Iowa, United States, 52804
    - Genesis Cancer Care Institute
  - Davenport, Iowa, United States, 52807
    - Iowa Cancer Specialists
  - 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
  - Iowa City, Iowa, United States, 52242
    - University of Iowa/Holden Comprehensive Cancer Center
  - West Des Moines, Iowa, United States, 50266-7700
    - Methodist West Hospital
  - West Des Moines, Iowa, United States, 50266
    - Mercy Medical Center-West Lakes
- Kansas
  - Dodge City, Kansas, United States, 67801
    - Cancer Center of Kansas - Dodge City
  - El Dorado, Kansas, United States, 67042
    - Cancer Center of Kansas - El Dorado
  - Garden City, Kansas, United States, 67846
    - Central Care Cancer Center - Garden City
  - Great Bend, Kansas, United States, 67530
    - Central Care Cancer Center - Great Bend
  - 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
  - Pittsburg, Kansas, United States, 66762
    - Ascension Via Christi - Pittsburg
  - Salina, Kansas, United States, 67401
    - Salina Regional Health Center
  - Salina, Kansas, United States, 67401
    - Cancer Center of Kansas - Salina
  - Topeka, Kansas, United States, 66606
    - University of Kansas Health System Saint Francis Campus
  - Topeka, Kansas, United States, 66606
    - Cotton O'Neil Cancer Center / Stormont Vail Health
  - Wellington, Kansas, United States, 67152
    - Cancer Center of Kansas - Wellington
  - 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, 67208
    - Cancer Center of Kansas-Wichita Medical Arts Tower
  - Wichita, Kansas, United States, 67214
    - Cancer Center of Kansas - Wichita
  - Wichita, Kansas, United States, 67208
    - Associates In Womens Health
  - Wichita, Kansas, United States, 67214
    - Wesley Medical Center
  - Winfield, Kansas, United States, 67156
    - Cancer Center of Kansas - Winfield
- Kentucky
  - Lexington, Kentucky, United States, 40504
    - Saint Joseph Radiation Oncology Resource Center
  - Lexington, Kentucky, United States, 40509
    - Saint Joseph Hospital East
  - Louisville, Kentucky, United States, 40202
    - Jewish Hospital
  - Louisville, Kentucky, United States, 40245
    - UofL Health Medical Center Northeast
- 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
  - Covington, Louisiana, United States, 70433
    - Mary Bird Perkins Cancer Center - Covington
  - Covington, Louisiana, United States, 70433
    - Northshore Oncology Associates-Covington
  - Houma, Louisiana, United States, 70360
    - Mary Bird Perkins Cancer Center - Houma
  - Houma, Louisiana, United States, 70360
    - Oncology Center of The South Incorporated
  - New Orleans, Louisiana, United States, 70121
    - Ochsner Medical Center Jefferson
- Maine
  - Bangor, Maine, United States, 04401
    - Eastern Maine Medical Center
  - Brewer, Maine, United States, 04412
    - Lafayette Family Cancer Center-EMMC
- Maryland
  - Baltimore, Maryland, United States, 21204
    - Greater Baltimore Medical Center
  - Salisbury, Maryland, United States, 21801
    - TidalHealth Peninsula Regional
- Massachusetts
  - Boston, Massachusetts, United States, 02215
    - Beth Israel Deaconess Medical Center
  - Boston, Massachusetts, United States, 02215
    - Dana-Farber Cancer Institute
  - Boston, Massachusetts, United States, 02115
    - Brigham and Women's Hospital
  - Boston, Massachusetts, United States, 02114
    - Massachusetts General Hospital Cancer Center
  - Pittsfield, Massachusetts, United States, 01201
    - Berkshire Medical Center - Cancer Center
- Michigan
  - Adrian, Michigan, United States, 49221
    - Hickman Cancer Center
  - Ann Arbor, Michigan, United States, 48109
    - University of Michigan Comprehensive Cancer Center
  - Ann Arbor, Michigan, United States, 48106
    - Saint Joseph Mercy Hospital
  - Battle Creek, Michigan, United States, 49017
    - Bronson Battle Creek
  - Bay City, Michigan, United States, 48706
    - McLaren Cancer Institute-Bay City
  - Brownstown, Michigan, United States, 48183
    - Henry Ford Cancer Institute-Downriver
  - 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, 48124
    - Beaumont Hospital - Dearborn
  - Detroit, Michigan, United States, 48202
    - Henry Ford Hospital
  - Detroit, Michigan, United States, 48201
    - Wayne State University/Karmanos Cancer Institute
  - Detroit, Michigan, United States, 48236
    - Ascension Saint John Hospital
  - Farmington Hills, Michigan, United States, 48334
    - Weisberg Cancer Treatment Center
  - Farmington Hills, Michigan, United States, 48336
    - Beaumont Hospital - Farmington Hills
  - Flint, Michigan, United States, 48532
    - McLaren Cancer Institute-Flint
  - Flint, Michigan, United States, 48532
    - Singh and Arora Hematology Oncology PC
  - Flint, Michigan, United States, 48503
    - Hurley Medical Center
  - Flint, Michigan, United States, 48503
    - Genesys Hurley Cancer Institute
  - 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
  - Jackson, Michigan, United States, 49201
    - Allegiance Health
  - Kalamazoo, Michigan, United States, 49007
    - West Michigan Cancer Center
  - Kalamazoo, Michigan, United States, 49007
    - Bronson Methodist Hospital
  - Kalamazoo, Michigan, United States, 49048
    - Borgess Medical Center
  - Lansing, Michigan, United States, 48912
    - Sparrow Hospital
  - Lansing, Michigan, United States, 48910
    - Karmanos Cancer Institute at McLaren Greater Lansing
  - Lapeer, Michigan, United States, 48446
    - McLaren Cancer Institute-Lapeer Region
  - Livonia, Michigan, United States, 48154
    - Trinity Health Saint Mary Mercy Livonia Hospital
  - Mount Clemens, Michigan, United States, 48043
    - McLaren Cancer Institute-Macomb
  - Mount Pleasant, Michigan, United States, 48858
    - McLaren Cancer Institute-Central Michigan
  - Muskegon, Michigan, United States, 49444
    - Trinity Health Muskegon Hospital
  - Niles, Michigan, United States, 49120
    - Lakeland Hospital Niles
  - Novi, Michigan, United States, 48374
    - Ascension Providence Hospitals - Novi
  - Owosso, Michigan, United States, 48867
    - McLaren Cancer Institute-Owosso
  - Petoskey, Michigan, United States, 49770
    - McLaren Cancer Institute-Northern Michigan
  - Pontiac, Michigan, United States, 48341
    - Saint Joseph Mercy Oakland
  - Pontiac, Michigan, United States, 48341
    - 21st Century Oncology-Pontiac
  - Port Huron, Michigan, United States, 48060
    - McLaren-Port Huron
  - Reed City, Michigan, United States, 49677
    - Spectrum Health Reed City Hospital
  - Royal Oak, Michigan, United States, 48073
    - William Beaumont Hospital-Royal Oak
  - Saginaw, Michigan, United States, 48601
    - Ascension Saint Mary's Hospital
  - Saint Joseph, Michigan, United States, 49085
    - Lakeland Medical Center Saint Joseph
  - Saint Joseph, Michigan, United States, 49085
    - Marie Yeager Cancer Center
  - Southfield, Michigan, United States, 48075
    - Ascension Providence Hospitals - Southfield
  - Traverse City, Michigan, United States, 49684
    - Munson Medical Center
  - Troy, Michigan, United States, 48085
    - William Beaumont Hospital - Troy
  - Warren, Michigan, United States, 48093
    - Saint John Macomb-Oakland Hospital
  - West Bloomfield, Michigan, United States, 48322
    - Henry Ford West Bloomfield Hospital
  - Wyoming, Michigan, United States, 49519
    - University of Michigan Health - West
- Minnesota
  - Bemidji, Minnesota, United States, 56601
    - Sanford Joe Lueken Cancer Center
  - Brainerd, Minnesota, United States, 56401
    - Essentia Health Saint Joseph's Medical Center
  - Burnsville, Minnesota, United States, 55337
    - Fairview Ridges Hospital
  - Coon Rapids, Minnesota, United States, 55433
    - Mercy Hospital
  - Deer River, Minnesota, United States, 56636
    - Essentia Health - Deer River Clinic
  - Detroit Lakes, Minnesota, United States, 56501
    - Essentia Health Saint Mary's - Detroit Lakes Clinic
  - Duluth, Minnesota, United States, 55805
    - Saint Luke's Hospital of Duluth
  - 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
  - Edina, Minnesota, United States, 55435
    - Fairview Southdale Hospital
  - Fergus Falls, Minnesota, United States, 56537
    - Lake Region Healthcare Corporation-Cancer Care
  - Fosston, Minnesota, United States, 56542
    - Essentia Health - Fosston
  - Fridley, Minnesota, United States, 55432
    - Unity Hospital
  - Hibbing, Minnesota, United States, 55746
    - Essentia Health Hibbing Clinic
  - Maple Grove, Minnesota, United States, 55369
    - Fairview Clinics and Surgery Center Maple Grove
  - Maplewood, Minnesota, United States, 55109
    - Saint John's Hospital - Healtheast
  - Maplewood, Minnesota, United States, 55109
    - Minnesota Oncology Hematology PA-Maplewood
  - Minneapolis, Minnesota, United States, 55415
    - Hennepin County Medical Center
  - Minneapolis, Minnesota, United States, 55407
    - Abbott-Northwestern Hospital
  - Minneapolis, Minnesota, United States, 55454
    - Health Partners Inc
  - Monticello, Minnesota, United States, 55362
    - Monticello Cancer Center
  - Park Rapids, Minnesota, United States, 56470
    - Essentia Health - Park Rapids
  - Robbinsdale, Minnesota, United States, 55422
    - North Memorial Medical Health Center
  - Rochester, Minnesota, United States, 55905
    - Mayo Clinic in Rochester
  - Saint Cloud, Minnesota, United States, 56303
    - Coborn Cancer Center at Saint Cloud Hospital
  - Saint Louis Park, Minnesota, United States, 55416
    - Park Nicollet Clinic - Saint Louis Park
  - Saint Paul, Minnesota, United States, 55101
    - Regions Hospital
  - Saint Paul, Minnesota, United States, 55102
    - United Hospital
  - Sandstone, Minnesota, United States, 55072
    - Essentia Health Sandstone
  - Shakopee, Minnesota, United States, 55379
    - Saint Francis Regional Medical Center
  - Stillwater, Minnesota, United States, 55082
    - Lakeview Hospital
  - Virginia, Minnesota, United States, 55792
    - Essentia Health Virginia Clinic
  - Waconia, Minnesota, United States, 55387
    - Ridgeview Medical Center
  - Willmar, Minnesota, United States, 56201
    - Rice Memorial Hospital
  - Woodbury, Minnesota, United States, 55125
    - Minnesota Oncology Hematology PA-Woodbury
- Mississippi
  - Grenada, Mississippi, United States, 38901
    - Baptist Cancer Center-Grenada
  - New Albany, Mississippi, United States, 38652
    - Baptist Memorial Hospital and Cancer Center-Union County
  - Oxford, Mississippi, United States, 38655
    - Baptist Memorial Hospital and Cancer Center-Oxford
  - Southhaven, Mississippi, United States, 38671
    - Baptist Memorial Hospital and Cancer Center-Desoto
- Missouri
  - Ballwin, Missouri, United States, 63011
    - Saint Louis Cancer and Breast Institute-Ballwin
  - Bolivar, Missouri, United States, 65613
    - Central Care Cancer Center - Bolivar
  - Bonne Terre, Missouri, United States, 63628
    - Parkland Health Center-Bonne Terre
  - Cape Girardeau, Missouri, United States, 63703
    - Saint Francis Medical Center
  - Cape Girardeau, Missouri, United States, 63703
    - Southeast Cancer Center
  - Jefferson City, Missouri, United States, 65109
    - Capital Region Southwest Campus
  - Joplin, Missouri, United States, 64804
    - Freeman Health System
  - Kansas City, Missouri, United States, 64154
    - University of Kansas Cancer Center - North
  - Kansas City, Missouri, United States, 64132
    - Research Medical Center
  - Lee's Summit, Missouri, United States, 64064
    - University of Kansas Cancer Center - Lee's Summit
  - Rolla, Missouri, United States, 65401
    - Delbert Day Cancer Institute at PCRMC
  - Rolla, Missouri, United States, 65401
    - Mercy Clinic-Rolla-Cancer and Hematology
  - Saint Joseph, Missouri, United States, 64506
    - Heartland Regional Medical Center
  - Saint Louis, Missouri, United States, 63131
    - Missouri Baptist Medical Center
  - Saint Louis, Missouri, United States, 63141
    - Mercy Hospital Saint Louis
  - Saint Louis, Missouri, United States, 63128
    - Mercy Hospital South
  - Sainte Genevieve, Missouri, United States, 63670
    - Sainte Genevieve County Memorial Hospital
  - Springfield, Missouri, United States, 65807
    - CoxHealth South Hospital
  - Springfield, Missouri, United States, 65804
    - Mercy Hospital Springfield
  - Sullivan, Missouri, United States, 63080
    - Missouri Baptist Sullivan Hospital
  - Sunset Hills, Missouri, United States, 63127
    - Missouri Baptist Outpatient Center-Sunset Hills
- Montana
  - Billings, Montana, United States, 59101
    - Billings Clinic Cancer Center
  - Billings, Montana, United States, 59101
    - Saint Vincent Healthcare
  - Bozeman, Montana, United States, 59715
    - Bozeman Deaconess Hospital
  - Butte, Montana, United States, 59701
    - Saint James Community Hospital and Cancer Treatment Center
  - Great Falls, Montana, United States, 59405
    - Great Falls Clinic
  - Great Falls, Montana, United States, 59405
    - Benefis Healthcare- Sletten Cancer Institute
  - Kalispell, Montana, United States, 59901
    - Kalispell Regional Medical Center
  - Missoula, Montana, United States, 59804
    - Community Medical Hospital
- Nebraska
  - Grand Island, Nebraska, United States, 68803
    - CHI Health Saint Francis
  - Kearney, Nebraska, United States, 68847
    - CHI Health Good Samaritan
  - Lincoln, Nebraska, United States, 68506
    - Nebraska Hematology and Oncology
  - Lincoln, Nebraska, United States, 68510
    - Nebraska Cancer Research Center
  - Lincoln, Nebraska, United States, 68516
    - Southeast Nebraska Cancer Center - 68th Street Place
  - Omaha, Nebraska, United States, 68124
    - Alegent Health Bergan Mercy Medical Center
  - Omaha, Nebraska, United States, 68122
    - Alegent Health Immanuel Medical Center
  - Omaha, Nebraska, United States, 68130
    - Alegent Health Lakeside Hospital
  - Omaha, Nebraska, United States, 68131
    - Creighton University Medical Center
  - Omaha, Nebraska, United States, 68124
    - Nebraska Cancer Specialists - Omaha
  - Scottsbluff, Nebraska, United States, 69361
    - Regional West Medical Center Cancer Center
- Nevada
  - Henderson, Nevada, United States, 89052
    - OptumCare Cancer Care at Seven Hills
  - Las Vegas, Nevada, United States, 89102
    - OptumCare Cancer Care at Charleston
  - Las Vegas, Nevada, United States, 89106
    - Radiation Oncology Centers of Nevada Central
  - Las Vegas, Nevada, United States, 89109
    - GenesisCare USA - Las Vegas
  - Las Vegas, Nevada, United States, 89128
    - OptumCare Cancer Care at MountainView
  - Las Vegas, Nevada, United States, 89148
    - Comprehensive Cancer Centers of Nevada
  - Las Vegas, Nevada, United States, 89148
    - OptumCare Cancer Care at Fort Apache
  - Reno, Nevada, United States, 89502
    - Renown Regional Medical Center
  - Reno, Nevada, United States, 89503
    - Saint Mary's Regional Medical Center
  - Reno, Nevada, United States, 89509
    - Radiation Oncology Associates
- New Hampshire
  - Lebanon, New Hampshire, United States, 03756
    - Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- New Jersey
  - Englewood, New Jersey, United States, 07631
    - Englewood Hospital and Medical Center
  - Moorestown, New Jersey, United States, 08057
    - Virtua Samson Cancer Center
  - Mount Holly, New Jersey, United States, 08060
    - Virtua Memorial
  - New Brunswick, New Jersey, United States, 08903
    - Rutgers Cancer Institute of New Jersey
  - Somerville, New Jersey, United States, 08876
    - Robert Wood Johnson University Hospital Somerset
  - Teaneck, New Jersey, United States, 07666
    - Holy Name Hospital
  - Voorhees, New Jersey, United States, 08043
    - Virtua Voorhees
- 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
  - Santa Fe, New Mexico, United States, 87505
    - Christus Saint Vincent Regional Cancer Center
- New York
  - Bay Shore, New York, United States, 11706
    - Northwell Health Imbert Cancer Center
  - Bronx, New York, United States, 10461
    - Montefiore Medical Center-Einstein Campus
  - Bronx, New York, United States, 10467
    - Montefiore Medical Center - Moses Campus
  - Bronx, New York, United States, 10461
    - Montefiore Medical Center-Weiler Hospital
  - Glens Falls, New York, United States, 12801
    - Glens Falls Hospital
  - Lake Success, New York, United States, 11042
    - Northwell Health/Center for Advanced Medicine
  - Manhasset, New York, United States, 11030
    - North Shore University Hospital
  - Middletown, New York, United States, 10940
    - Garnet Health Medical Center
  - New Hyde Park, New York, United States, 11040
    - Long Island Jewish Medical Center
  - New York, New York, United States, 10016
    - Laura and Isaac Perlmutter Cancer Center at NYU Langone
  - Rochester, New York, United States, 14642
    - University of Rochester
  - Staten Island, New York, United States, 10305
    - Staten Island University Hospital
  - Syracuse, New York, United States, 13210
    - State University of New York Upstate Medical University
- North Carolina
  - Albemarle, North Carolina, United States, 28002
    - Atrium Health Stanly/LCI-Albemarle
  - Asheville, North Carolina, United States, 28801
    - Mission Hospital
  - 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
  - Concord, North Carolina, United States, 28025
    - Atrium Health Cabarrus/LCI-Concord
  - Huntersville, North Carolina, United States, 28078
    - Novant Health Presbyterian Medical Center Huntersville
  - Matthews, North Carolina, United States, 28105
    - Matthews Radiation Oncology Center
  - Monroe, North Carolina, United States, 28112
    - Atrium Health Union/LCI-Union
  - Raleigh, North Carolina, United States, 27607
    - UNC Rex Healthcare
  - Shelby, North Carolina, United States, 28150
    - Atrium Health Cleveland/LCI-Cleveland
  - Winston-Salem, North Carolina, United States, 27157
    - Wake Forest University Health Sciences
- 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, 58103
    - Essentia Health Cancer Center-South University Clinic
  - Fargo, North Dakota, United States, 58122
    - Sanford Broadway Medical Center
  - Jamestown, North Dakota, United States, 58401
    - Essentia Health - Jamestown Clinic
- Ohio
  - Akron, Ohio, United States, 44307
    - Cleveland Clinic Akron General
  - Beachwood, Ohio, United States, 44122
    - UHHS-Chagrin Highlands Medical Center
  - Beavercreek, Ohio, United States, 45431
    - Indu and Raj Soin Medical Center
  - Canton, Ohio, United States, 44708
    - Cleveland Clinic Mercy Hospital
  - Centerville, Ohio, United States, 45459
    - Miami Valley Hospital South
  - Centerville, Ohio, United States, 45459
    - Dayton Physicians LLC-Miami Valley South
  - Chardon, Ohio, United States, 44024
    - Geauga Hospital
  - Cincinnati, Ohio, United States, 45219
    - University of Cincinnati Cancer Center-UC Medical Center
  - Cincinnati, Ohio, United States, 45220
    - Good Samaritan Hospital - Cincinnati
  - Cincinnati, Ohio, United States, 45242
    - Bethesda North Hospital
  - Cincinnati, Ohio, United States, 45236
    - Oncology Hematology Care Inc-Kenwood
  - Cleveland, Ohio, United States, 44106
    - Case Western Reserve University
  - Columbus, Ohio, United States, 43210
    - Ohio State University Comprehensive Cancer Center
  - Dayton, Ohio, United States, 45406
    - Good Samaritan Hospital - Dayton
  - Dayton, Ohio, United States, 45409
    - Miami Valley Hospital
  - Dayton, Ohio, United States, 45415
    - Dayton Physician LLC-Miami Valley Hospital North
  - Dayton, Ohio, United States, 45415
    - Miami Valley Hospital North
  - Elyria, Ohio, United States, 44035
    - Mercy Cancer Center-Elyria
  - Findlay, Ohio, United States, 45840
    - Blanchard Valley Hospital
  - Findlay, Ohio, United States, 45840
    - Armes Family Cancer Center
  - Findlay, Ohio, United States, 45840
    - Orion Cancer Care
  - Franklin, Ohio, United States, 45005-1066
    - Atrium Medical Center-Middletown Regional Hospital
  - Franklin, Ohio, United States, 45005
    - Dayton Physicians LLC-Atrium
  - Greenville, Ohio, United States, 45331
    - Wayne Hospital
  - Greenville, Ohio, United States, 45331
    - Dayton Physicians LLC-Wayne
  - Kettering, Ohio, United States, 45429
    - Kettering Medical Center
  - Kettering, Ohio, United States, 45409
    - Greater Dayton Cancer Center
  - Maumee, Ohio, United States, 43537
    - Toledo Clinic Cancer Centers-Maumee
  - 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
  - Ravenna, Ohio, United States, 44266
    - University Hospitals Portage Medical Center
  - Sandusky, Ohio, United States, 44870
    - UH Seidman Cancer Center at Firelands Regional Medical Center
  - Springfield, Ohio, United States, 45505
    - Springfield Regional Medical Center
  - Springfield, Ohio, United States, 45504
    - Springfield Regional Cancer Center
  - Sylvania, Ohio, United States, 43560
    - ProMedica Flower Hospital
  - Toledo, Ohio, United States, 43606
    - ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
  - Toledo, Ohio, United States, 43623
    - Mercy Health - Saint Anne Hospital
  - Toledo, Ohio, United States, 43623
    - Toledo Clinic Cancer Centers-Toledo
  - Troy, Ohio, United States, 45373
    - Upper Valley Medical Center
  - Troy, Ohio, United States, 45373
    - Dayton Physicians LLC - Troy
  - Wadsworth, Ohio, United States, 44281
    - University Hospitals Sharon Health 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
- Oklahoma
  - Lawton, Oklahoma, United States, 73505
    - Cancer Centers of Southwest Oklahoma Research
  - Oklahoma City, Oklahoma, United States, 73104
    - University of Oklahoma Health Sciences Center
  - Oklahoma City, Oklahoma, United States, 73120
    - Mercy Hospital Oklahoma City
  - Oklahoma City, Oklahoma, United States, 73109
    - Integris Southwest Medical Center
  - Oklahoma City, Oklahoma, United States, 73142
    - Integris Cancer Institute of Oklahoma
- Oregon
  - Gresham, Oregon, United States, 97030
    - Legacy Mount Hood Medical Center
  - Portland, Oregon, United States, 97210
    - Legacy Good Samaritan Hospital and Medical Center
  - Portland, Oregon, United States, 97227
    - Kaiser Permanente Northwest
- Pennsylvania
  - Abington, Pennsylvania, United States, 19001
    - Jefferson Abington Hospital
  - Allentown, Pennsylvania, United States, 18103
    - Lehigh Valley Hospital-Cedar Crest
  - Bethlehem, Pennsylvania, United States, 18017
    - Lehigh Valley Hospital - Muhlenberg
  - Broomall, Pennsylvania, United States, 19008
    - Crozer-Keystone Regional Cancer Center at Broomall
  - Chadds Ford, Pennsylvania, United States, 19317
    - Christiana Care Health System-Concord Health Center
  - Danville, Pennsylvania, United States, 17822
    - Geisinger Medical Center
  - Dunmore, Pennsylvania, United States, 18512
    - Northeast Radiation Oncology Center
  - East Stroudsburg, Pennsylvania, United States, 18301
    - Pocono Medical Center
  - Erie, Pennsylvania, United States, 16544
    - Saint Vincent Hospital
  - Glen Mills, Pennsylvania, United States, 19342
    - Crozer Regional Cancer Center at Brinton Lake
  - Jefferson Hills, Pennsylvania, United States, 15025
    - Jefferson Hospital
  - Lewisburg, Pennsylvania, United States, 17837
    - Geisinger Medical Oncology-Lewisburg
  - Lewistown, Pennsylvania, United States, 17044
    - Lewistown Hospital
  - Monroeville, Pennsylvania, United States, 15146
    - Forbes Hospital
  - Philadelphia, Pennsylvania, United States, 19111
    - Fox Chase Cancer Center
  - Philadelphia, Pennsylvania, United States, 19107
    - Thomas Jefferson University Hospital
  - Philadelphia, Pennsylvania, United States, 19140
    - Temple University Hospital
  - Pittsburgh, Pennsylvania, United States, 15212
    - Allegheny General Hospital
  - Selinsgrove, Pennsylvania, United States, 17870
    - Geisinger Medical Oncology-Selinsgrove
  - Sellersville, Pennsylvania, United States, 18960
    - Grand View Hospital
  - West Reading, Pennsylvania, United States, 19611
    - Reading Hospital
  - Wilkes-Barre, Pennsylvania, United States, 18711
    - Geisinger Wyoming Valley/Henry Cancer Center
  - Willow Grove, Pennsylvania, United States, 19090
    - Asplundh Cancer Pavilion
  - Wynnewood, Pennsylvania, United States, 19096
    - Lankenau Medical Center
- South Carolina
  - Anderson, South Carolina, United States, 29621
    - AnMed Health Cancer Center
  - Boiling Springs, South Carolina, United States, 29316
    - Prisma Health Cancer Institute - Spartanburg
  - Charleston, South Carolina, United States, 29425
    - Medical University of South Carolina
  - Gaffney, South Carolina, United States, 29341
    - Gibbs Cancer Center-Gaffney
  - Greenville, South Carolina, United States, 29605
    - Prisma Health Cancer Institute - Faris
  - Greenville, South Carolina, United States, 29615
    - Prisma Health Cancer Institute - Eastside
  - 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
  - Aberdeen, South Dakota, United States, 57401
    - Avera Cancer Institute-Aberdeen
  - 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
  - Chattanooga, Tennessee, United States, 37404
    - Memorial Hospital
  - Collierville, Tennessee, United States, 38017
    - Baptist Memorial Hospital and Cancer Center-Collierville
  - Germantown, Tennessee, United States, 38138
    - The West Clinic - Wolf River
  - Memphis, Tennessee, United States, 38120
    - Baptist Memorial Hospital and Cancer Center-Memphis
  - Memphis, Tennessee, United States, 38163
    - University of Tennessee Health Science Center
  - Memphis, Tennessee, United States, 38104
    - The West Clinic - Mid-Town
  - Nashville, Tennessee, United States, 37232
    - Vanderbilt University/Ingram Cancer Center
  - Nashville, Tennessee, United States, 37204
    - Vanderbilt Breast Center at One Hundred Oaks
- Texas
  - Bryan, Texas, United States, 77802
    - Saint Joseph Regional Cancer Center
  - Dallas, Texas, United States, 75235
    - Parkland Memorial Hospital
  - Dallas, Texas, United States, 75390
    - UT Southwestern/Simmons Cancer Center-Dallas
  - Dallas, Texas, United States, 75246
    - Baylor University Medical Center
  - Galveston, Texas, United States, 77555-0565
    - University of Texas Medical Branch
  - Houston, Texas, United States, 77030
    - M D Anderson Cancer Center
  - Houston, Texas, United States, 77030
    - Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
  - Houston, Texas, United States, 77030
    - Ben Taub General Hospital
  - League City, Texas, United States, 77573
    - UTMB Cancer Center at Victory Lakes
  - Lubbock, Texas, United States, 79410
    - Covenant Medical Center-Lakeside
  - Temple, Texas, United States, 76508
    - Scott and White Memorial Hospital
- Utah
  - Cedar City, Utah, United States, 84720
    - Sandra L Maxwell Cancer 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, 84106
    - Utah Cancer Specialists-Salt Lake City
  - Salt Lake City, Utah, United States, 84143
    - LDS Hospital
- Vermont
  - Berlin, Vermont, United States, 05602
    - Central Vermont Medical Center/National Life Cancer Treatment
  - Burlington, Vermont, United States, 05401
    - University of Vermont Medical Center
  - Burlington, Vermont, United States, 05405
    - University of Vermont and State Agricultural College
  - Saint Johnsbury, Vermont, United States, 05819
    - Norris Cotton Cancer Center-North
- Virginia
  - Hampton, Virginia, United States, 23666
    - Sentara Cancer Institute at Sentara CarePlex Hospital
  - Norfolk, Virginia, United States, 23507
    - Sentara Norfolk General Hospital
  - Norfolk, Virginia, United States, 23502
    - Sentara Leigh Hospital
  - Richmond, Virginia, United States, 23298
    - Virginia Commonwealth University/Massey Cancer Center
- Washington
  - Auburn, Washington, United States, 98001
    - MultiCare Auburn Medical Center
  - Bellevue, Washington, United States, 98004
    - Overlake Medical Center
  - Bremerton, Washington, United States, 98310
    - Harrison HealthPartners Hematology and Oncology-Bremerton
  - Bremerton, Washington, United States, 98310
    - Harrison Medical Center
  - Burien, Washington, United States, 98166
    - Highline Medical Center-Main Campus
  - Federal Way, Washington, United States, 98002
    - Virginia Mason Federal Way Medical Center
  - Gig Harbor, Washington, United States, 98332
    - Tacoma/Valley Radiation Oncology Centers-Gig Harbor
  - Gig Harbor, Washington, United States, 98335
    - MultiCare Gig Harbor Medical Park
  - Kennewick, Washington, United States, 99336
    - Tri-Cities Cancer Center
  - Kirkland, Washington, United States, 98034
    - Seattle Cancer Care Alliance at EvergreenHealth
  - Mount Vernon, Washington, United States, 98274
    - Skagit Valley Hospital
  - Mount Vernon, Washington, United States, 98274
    - Skagit Regional Health Cancer Care Center
  - Puyallup, Washington, United States, 98372
    - MultiCare Good Samaritan Hospital
  - Puyallup, Washington, United States, 98372
    - Tacoma/Valley Radiation Oncology Centers-Puyallup
  - Renton, Washington, United States, 98055
    - Valley Medical Center
  - Seattle, Washington, United States, 98109
    - Fred Hutchinson Cancer Research Center
  - Seattle, Washington, United States, 98101
    - Virginia Mason Medical Center
  - Seattle, Washington, United States, 98195
    - University of Washington Medical Center - Montlake
  - Seattle, Washington, United States, 98109
    - FHCC South Lake Union
  - Seattle, Washington, United States, 98133
    - FHCC at Northwest Hospital
  - Spokane, Washington, United States, 99208
    - Spokane Valley Cancer Center-Mayfair
  - Tacoma, Washington, United States, 98405
    - Northwest Medical Specialties PLLC
  - Tacoma, Washington, United States, 98405
    - MultiCare Tacoma General Hospital
  - Tacoma, Washington, United States, 98405
    - Tacoma/Valley Radiation Oncology Centers-Saint Joe's
  - Vancouver, Washington, United States, 98686
    - Legacy Salmon Creek Hospital
  - Wenatchee, Washington, United States, 98801
    - Wenatchee Valley Hospital and Clinics
  - Yakima, Washington, United States, 98902
    - North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
- West Virginia
  - Bridgeport, West Virginia, United States, 26330
    - United Hospital Center
  - Charleston, West Virginia, United States, 25304
    - West Virginia University Charleston Division
  - Morgantown, West Virginia, United States, 26506
    - West Virginia University Healthcare
  - Parkersburg, West Virginia, United States, 26101
    - Camden Clark Medical Center
  - Wheeling, West Virginia, United States, 26003
    - Wheeling Hospital/Schiffler Cancer Center
- Wisconsin
  - Ashland, Wisconsin, United States, 54806
    - Duluth Clinic Ashland
  - Ashland, Wisconsin, United States, 54806
    - Northwest Wisconsin Cancer Center
  - Burlington, Wisconsin, United States, 53105
    - Aurora Cancer Care-Southern Lakes VLCC
  - Eau Claire, Wisconsin, United States, 54701
    - Marshfield Medical Center-EC Cancer Center
  - Eau Claire, Wisconsin, United States, 54701
    - Marshfield Clinic Cancer Center at Sacred Heart
  - Fond Du Lac, Wisconsin, United States, 54937
    - Aurora Health Center-Fond du Lac
  - 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
  - Johnson Creek, Wisconsin, United States, 53038
    - UW Cancer Center Johnson Creek
  - Kenosha, Wisconsin, United States, 53142
    - Aurora Cancer Care-Kenosha South
  - Madison, Wisconsin, United States, 53792
    - University of Wisconsin Carbone Cancer 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
  - 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
  - Minocqua, Wisconsin, United States, 54548
    - Marshfield Clinic-Minocqua Center
  - Mukwonago, Wisconsin, United States, 53149
    - ProHealth D N Greenwald Center
  - New Richmond, Wisconsin, United States, 54017
    - Cancer Center of Western Wisconsin
  - Oconomowoc, Wisconsin, United States, 53066
    - ProHealth Oconomowoc Memorial Hospital
  - Oshkosh, Wisconsin, United States, 54904
    - Vince Lombardi Cancer Clinic - Oshkosh
  - Racine, Wisconsin, United States, 53406
    - Aurora Cancer Care-Racine
  - Rice Lake, Wisconsin, United States, 54868
    - Marshfield Medical Center-Rice Lake
  - Sheboygan, Wisconsin, United States, 53081
    - Vince Lombardi Cancer Clinic-Sheboygan
  - Stevens Point, Wisconsin, United States, 54482
    - Marshfield Medical Center-River Region at Stevens Point
  - Summit, Wisconsin, United States, 53066
    - Aurora Medical Center in Summit
  - Two Rivers, Wisconsin, United States, 54241
    - Vince Lombardi Cancer Clinic-Two Rivers
  - Waukesha, Wisconsin, United States, 53188
    - UW Cancer Center at ProHealth Care
  - Wausau, Wisconsin, United States, 54401
    - Marshfield Clinic-Wausau Center
  - Wauwatosa, Wisconsin, United States, 53226
    - Aurora Cancer Care-Milwaukee West
  - 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
  - Weston, Wisconsin, United States, 54476
    - Diagnostic and Treatment Center

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

Description

Inclusion Criteria:

The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Diagnosis of adenocarcinoma of the rectum with the major portion of the tumor intact; Note: prior to randomization, the investigator must specify and document each of the following:
- Distance of the lowest tumor margin from the anal verge; and
- Intent for sphincter sparing or non-sphincter sparing surgical resection according to the primary surgeon; and
- The majority of the untreated tumor must be < 12 cm from the anal verge or below the peritoneal reflection as determined by the treating surgeon
The tumor must be clinically determined to be locally advanced stage II or stage III rectal cancer, and must also meet any ONE of the following criteria:
- Distal location (as defined by measurement on magnetic resonance imaging [MRI], transrectal ultrasound [ERUS]/pelvic computed tomography [CT] [with IV contrast] scan or palpable on digital rectal examination [DRE]): cT3-4 =< 5 cm from the anal verge, any N
- Bulky: any cT4 or evidence that the tumor is adjacent to (defined as within 3 mm of) the mesorectal fascia on MRI or ERUS/pelvic CT (with IV contrast) scan
- High risk for metastatic disease with 4 or more regional lymph nodes (cN2); clinical nodal or "cN" status for eligibility includes the total number of nodes (N2 = 4 or more) in the mesorectal and superior rectal stations measuring >= 1.0 cm in any axis on cross sectional or endoscopic imaging; Note: nodes must measure 1.0 cm or greater to be considered positive for this eligibility requirement
- Not a candidate for sphincter-sparing surgical resection prior to neoadjuvant therapy (as planned by the primary surgeon)
  - Note: clinical stage of the primary tumor and nodes may be determined locally by rectal endoscopic ultrasound or pelvic MRI (pelvic MRI is strongly preferred); CT scan with IV contrast is acceptable provided there is evidence of T4 and/or N2 disease
Patients must have the ability to swallow and retain oral medication
Absolute neutrophil count (ANC) must be >= 1200/mm^3 (within 28 days before randomization)
Platelet count must be >= 100,000/mm^3 (within 28 days before randomization)
Hemoglobin must be >= 10 g/dL (within 28 days before randomization)
Total bilirubin must be =< ULN (upper limit of normal) for the lab unless the patient has a bilirubin elevation > ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin (within 28 days before randomization)
Alkaline phosphatase must be =< 3 x ULN for the lab (within 28 days before randomization)
Aspartate aminotransferase (AST) must be =< 3 x ULN for the lab (within 28 days before randomization);
- Note: if alanine aminotransferase (ALT) is performed instead of AST (per institution's standard practice), the ALT value must be =< 3 x ULN; if both were performed, the AST must also be =< 3 x ULN; if AST and/or ALT is >= ULN but =< 3 x ULN, serologic testing for hepatitis B and C must be performed and results for viral infection must be negative
Serum creatinine =< ULN for the lab and measured or calculated creatinine clearance > 60 mL/min (within 28 days before randomization)
Serum potassium, magnesium, and calcium levels within 28 days before randomization must be within normal limits (WNL) for the lab
International normalized ratio of prothrombin time (INR) within 28 days before randomization must be =< ULN for the lab; patients who are therapeutically treated with an agent such as warfarin may participate if they are on a stable dose and no underlying abnormality in coagulation parameters exists per medical history
Patients with acquired immunodeficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease must:
- Have a cluster of differentiation (CD)4 count >= 200 cells/uL within 30 days before beginning study therapy
- Be off all antiretroviral therapy (prophylaxis/treatment) more than 60 days before beginning study therapy, and
- Have no evidence of opportunistic infections
Pregnancy test (urine or serum beta-human chorionic gonadotropin [HCG]) done within 72 hours before randomization must be negative (for women of childbearing potential only); if urine pregnancy results are positive or cannot be confirmed as negative, a serum pregnancy test will be required

Exclusion Criteria:

Rectal cancer histology other than adenocarcinoma (i.e., sarcoma, lymphoma, squamous cell carcinoma, mucosal melanoma, etc.)
Definitive clinical or radiologic evidence of metastatic disease; required imaging studies must have been performed within 28 days prior to randomization; Note: Distant clinical staging to exclude patients with overt metastatic disease is determined by:
- Chest: CT scan (preferred); chest x-ray posterioranterior (PA) and lateral (acceptable); or positron emission tomography (PET) scan (acceptable)
- Abdomen: CT scan with IV contrast (preferred); or MRI (acceptable)
- Pelvis: MRI (preferred) or CT scan with IV contrast (acceptable)
  - (It is recommended that the same imaging tests that are performed before randomization be used at follow-up time points; Note: CT scans of the abdomen and pelvis must be performed with IV contrast)
History of prior invasive rectal malignancy, regardless of disease-free interval
Cardiac disease that would preclude the use of any of the drugs included in the GI002 treatment regimen; this includes but is not limited to:
- Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker
- Ventricular tachycardia or supraventricular tachycardia that requires treatment with class Ia antiarrhythmic drugs (e.g., quinidine, procainamide, disopyramide) or class III antiarrhythmic drug (e.g., sotalol, amiodarone, dofetilide); use of other antiarrhythmic drugs is permitted
- Second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker
- Complete left bundle branch block (LBBB)
- History of long QT syndrome
- Corrected QT (QTc) >= 450 ms
Sensory or motor neuropathy >= grade 2
History of, or any evidence of active, non-infectious pneumonitis
Active inflammatory bowel disease (i.e., patients requiring current medical interventions or who are symptomatic) or have a history of abdominal surgery or other medical condition that may, in the opinion of the treating physician, interfere with gastrointestinal motility or absorption
Active autoimmune disease that has required systemic treatment within the past 2 years (i.e., with use of modifying agents, corticosteroids, or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
History of active TB (Bacillus tuberculosis)
Active or chronic infection requiring systemic therapy
Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy; the use of physiologic doses of corticosteroids may be approved after consultation with the study principal investigator (PI)
Active seizure disorder uncontrolled by medication
Any antineoplastic therapy for this cancer before randomization
Synchronous colon cancer
Other invasive cancer within 5 years before randomization; exceptions are colonic polyps, non-melanoma skin cancer or carcinoma-in-situ of the cervix
Antineoplastic therapy (e.g. chemotherapy or targeted therapy) for other invasive cancer within 5 years before randomization; (for the purposes of this study, hormonal therapy is not considered chemotherapy)
Prior treatment with an investigational compound being tested in this study (e.g., poly ADP ribose polymerase [PARP] inhibitor, anti-PD-1, anti-PD-L1, or anti-PD-L2)
Receipt of live vaccination within 28 days before randomization; seasonal flu vaccines that do not contain live virus are permitted
Major surgery within 4 weeks before randomization
Any therapeutic pelvic radiation
Known homozygous DPD (dihydro pyrimidine dehydrogenase) deficiency
Any of the following because this study involves agents that have known or potential genotoxic or mutagenic, and teratogenic effects:
- Pregnant women
- Nursing women who are unwilling to discontinue nursing
- Men or women of childbearing potential who are unwilling to employ adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) for the duration of study treatment and for 4 months after the last dose of study therapy
Co-morbid illnesses or other concurrent disease that, in the judgement of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens or prevent required follow-up

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)

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm II (mFOLFOX6, RT, capecitabine, veliparib) Patients receive mFOLFOX6 regimen consisting of oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 2 weeks for up to 8 cycles in the absence of disease progression or unacceptable toxicity. 3-4 weeks after last does of mFOLFOX6 patient undergo RT and receive capecitabine PO BID and veliparib PO BID Monday-Friday for 5 weeks in the absence of disease progression or unacceptable toxicity.	Drug: Fluorouracil Given IV Other Names: 5-Fluracil Fluracil 5 Fluorouracil 5 Fluorouracilum 5 FU 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fu 5FU AccuSite Carac Fluoro Uracil Fluouracil Flurablastin Fluracedyl Fluril Fluroblastin Ribofluor Ro 2-9757 Ro-2-9757 Drug: Leucovorin Given IV Other Names: Folinic acid Drug: Oxaliplatin Given IV Other Names: 1-OHP Dacotin Dacplat Eloxatin Ai Heng Aiheng Diaminocyclohexane Oxalatoplatinum Eloxatine JM-83 Oxalatoplatin Oxalatoplatinum RP 54780 RP-54780 SR-96669 Drug: Capecitabine Given PO Other Names: Xeloda Ro 09-1978/000 Drug: Veliparib Given PO Other Names: ABT-888 PARP-1 inhibitor ABT-888 Radiation: Intensity-Modulated Radiation Therapy Undergo intensity modulated radiation therapy Other Names: IMRT Intensity Modulated RT Intensity-Modulated Radiotherapy Radiation, Intensity-Modulated Radiotherapy Intensity modulated radiation therapy (procedure)
Experimental: Arm III (mFOLFOX6, RT, capecitabine, pembrolizumab) ARM III: Patients receive mFOLFOX6 regimen consisting of oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. 3-4 weeks after last does of mFOLFOX6 patient undergo RT and receive capecitabine PO BID Monday-Friday for 5 weeks. They also receive pembrolizumab IV over 30 minutes every 3 weeks beginning on day 1 of RT for up to 6 cycles in the absence of disease progression or unacceptable toxicity.	Biological: Pembrolizumab Given IV Other Names: Keytruda MK-3475 Lambrolizumab SCH 900475 BCD-201 Pembrolizumab Biosimilar BCD-201 Drug: Fluorouracil Given IV Other Names: 5-Fluracil Fluracil 5 Fluorouracil 5 Fluorouracilum 5 FU 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fu 5FU AccuSite Carac Fluoro Uracil Fluouracil Flurablastin Fluracedyl Fluril Fluroblastin Ribofluor Ro 2-9757 Ro-2-9757 Drug: Leucovorin Given IV Other Names: Folinic acid Drug: Oxaliplatin Given IV Other Names: 1-OHP Dacotin Dacplat Eloxatin Ai Heng Aiheng Diaminocyclohexane Oxalatoplatinum Eloxatine JM-83 Oxalatoplatin Oxalatoplatinum RP 54780 RP-54780 SR-96669 Drug: Capecitabine Given PO Other Names: Xeloda Ro 09-1978/000 Radiation: Intensity-Modulated Radiation Therapy Undergo intensity modulated radiation therapy Other Names: IMRT Intensity Modulated RT Intensity-Modulated Radiotherapy Radiation, Intensity-Modulated Radiotherapy Intensity modulated radiation therapy (procedure)
Active Comparator: Arm I (mFOLFOX6, RT, capecitabine) Patients receive mFOLFOX6 regimen consisting of oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. 3-4 weeks after last does of mFOLFOX6 patient undergo RT and receive capecitabine PO BID Monday-Friday for 5 weeks in the absence of disease progression or unacceptable toxicity. Participants assigned to Arm I concurrently with Arm II or with Arm III.	Drug: Fluorouracil Given IV Other Names: 5-Fluracil Fluracil 5 Fluorouracil 5 Fluorouracilum 5 FU 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fu 5FU AccuSite Carac Fluoro Uracil Fluouracil Flurablastin Fluracedyl Fluril Fluroblastin Ribofluor Ro 2-9757 Ro-2-9757 Drug: Leucovorin Given IV Other Names: Folinic acid Drug: Oxaliplatin Given IV Other Names: 1-OHP Dacotin Dacplat Eloxatin Ai Heng Aiheng Diaminocyclohexane Oxalatoplatinum Eloxatine JM-83 Oxalatoplatin Oxalatoplatinum RP 54780 RP-54780 SR-96669 Drug: Capecitabine Given PO Other Names: Xeloda Ro 09-1978/000 Radiation: Intensity-Modulated Radiation Therapy Undergo intensity modulated radiation therapy Other Names: IMRT Intensity Modulated RT Intensity-Modulated Radiotherapy Radiation, Intensity-Modulated Radiotherapy Intensity modulated radiation therapy (procedure)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neoadjuvant Rectal Cancer (NAR) Score Time Frame: Baseline to up to 3 years	A linear regression model that controls for the stratification factors (cT-stage and cN-stage) will be used. Mean NAR scores along with standard errors and confidence intervals will be reported by treatment. The NAR score ranges from zero to 100 with lower values corresponding to better prognosis.	Baseline to up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival Time Frame: Time from start of study treatment, assessed up to 3 years	Analyzed using the stratified log rank test with strata cT-stage and cN-stage. Kaplan-Meier plots will illustrate the distribution of these endpoints by treatment. Cox regression models will be used to estimate hazard ratios and associated confidence intervals.	Time from start of study treatment, assessed up to 3 years
Disease Free Survival Time Frame: Time from start of study treatment, assessed up to 3 years	Analyzed using the stratified log rank test with strata cT-stage and cN-stage. Kaplan-Meier plots will illustrate the distribution of these endpoints by treatment. Cox regression models will be used to estimate hazard ratios and associated confidence intervals.	Time from start of study treatment, assessed up to 3 years
Rate of Pathologic Complete Response (Nodes and Tumor) ypT0 and ypN0 Time Frame: Up to 3 years	Pathologic Complete Response means no remaining cancer detectable in the pathology sample. Analyzed by a logistic regression model that controls for the stratification factors (cT-stage and cN-stage). Observed proportions along with confidence intervals will be presented by treatment.	Up to 3 years
Rate of Sphincter Preservation Time Frame: Up to 3 years	Sphincter preservation means that the surgical procedure used to remove the tumor did not disturb the sphincter muscle. Analyzed by a logistic regression model that controls for the stratification factors (cT-stage and cN-stage). Observed proportions along with confidence intervals will be presented by treatment.	Up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients Who Have a Tumor Resection Overall (and Conditional on Beginning Induction Chemotherapy, and Conditional on Beginning Chemoradiotherapy) Time Frame: Up to 3 years	Analyzed by a logistic regression model that controls for the stratification factors (cT-stage and cN-stage). Observed proportions along with confidence intervals will be presented by treatment.	Up to 3 years
Time From Initiation of Chemoradiotherapy to Surgery in the Subset of Patients With Tumor Resection Time Frame: Up to 3 years	Analyzed using the stratified log rank test with strata cT-stage and cN-stage. Kaplan-Meier plots will illustrate the distribution of time to surgery (TTS) by treatment. Cox regression models will be used to estimate hazard ratios and associated confidence intervals.	Up to 3 years
Rate of Disease Progression During Chemotherapy (Prior to Chemoradiation) Time Frame: Up to 3 years	Analyzed by a logistic regression model that controls for the stratification factors (cT-stage and cN-stage). Observed proportions along with confidence intervals will be presented by treatment.	Up to 3 years
Rate of Clinical Complete Response Rate, ycT0 Time Frame: Up to 3 years	Analyzed by a logistic regression model that controls for the stratification factors (cT-stage and cN-stage). Observed proportions along with confidence intervals will be presented by treatment.	Up to 3 years
Rate of Negative Circumferential Margin Time Frame: Up to 3 years	Analyzed by a logistic regression model that controls for the stratification factors (cT-stage and cN-stage). Observed proportions along with confidence intervals will be presented by treatment.	Up to 3 years
Rate of Completion of All Cycles of Neoadjuvant Chemotherapy Time Frame: Up to 3 years	Analyzed by a logistic regression model that controls for the stratification factors (cT-stage and cN-stage). Observed proportions along with confidence intervals will be presented by treatment.	Up to 3 years
Rate of Completion of Full Course of Chemoradiation Time Frame: Up to 3 years	Analyzed by a logistic regression model that controls for the stratification factors (cT-stage and cN-stage). Observed proportions along with confidence intervals will be presented by treatment.	Up to 3 years
Incidence of Toxicity Including Patient-reported Toxicities Time Frame: 30 days after last study treatment	Will be assessed using Common Terminology for Adverse Events (CTCAE) version 4.0 (CTCAE version 5.0 beginning April 1, 2018).	30 days after last study treatment
Correlative Molecular Predictors of Response and Distant Failure Time Frame: Up to 3 years	Cox regression models will be used to evaluate markers for time-to-event variables. Logistic regression models will be used for binary variables. Models will control for stratification factors and possibly other prognostic variables (e.g. gender or treatment).	Up to 3 years
Relationship Between Radiographic Findings and Pathologic Outcomes Time Frame: Up to 3 years	Will explore the relationship between radiographic findings and pathologic outcomes.	Up to 3 years

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: Thomas J George, NRG Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Rahma OE, Yothers G, Hong TS, Russell MM, You YN, Parker W, Jacobs SA, Colangelo LH, Lucas PC, Gollub MJ, Hall WA, Kachnic LA, Vijayvergia N, O'Rourke MA, Faller BA, Valicenti RK, Schefter TE, George S, Kainthla R, Stella PJ, Sigurdson E, Wolmark N, George TJ. Use of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Initial Results From the Pembrolizumab Arm of a Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021 Aug 1;7(8):1225-1230. doi: 10.1001/jamaoncol.2021.1683. Erratum In: JAMA Oncol. 2022 Jul 1;8(7):1073.

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)

January 11, 2017

Primary Completion (Actual)

April 21, 2020

Study Completion (Actual)

September 20, 2023

Study Registration Dates

First Submitted

September 30, 2016

First Submitted That Met QC Criteria

September 30, 2016

First Posted (Estimated)

October 3, 2016

Study Record Updates

Last Update Posted (Actual)

October 12, 2023

Last Update Submitted That Met QC Criteria

September 21, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

NCI-2016-00222 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
U10CA180868 (U.S. NIH Grant/Contract)
NRG-GI002 (Other Identifier: CTEP)
s17-00197

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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United States, France, Italy, United Kingdom, Spain, Belgium, Israel, Mexico, Japan, Canada, Netherlands, Sweden, Korea, Republic of, Australia, Russian Federation, Chile, Germany, Poland, Ireland, New Zealand, Denmark, Switzerland, South Africa
Merck Sharp & Dohme LLC

Completed

Relative Bioavailability Study of Subcutaneous Injection Versus Intravenous Infusion of Pembrolizumab (MK-3475) in Participants With Advanced Melanoma (MK-3475-555/KEYNOTE-555)

Melanoma

Australia, South Africa, Spain, Sweden
Acerta Pharma BV
Merck Sharp & Dohme LLC

Completed

Study of the Combination of ACP-196 and Pembrolizumab in Subjects With Platinum Resistant Urothelial Bladder Cancer (KEYNOTE143)

Metastatic Urothelial Carcinoma

United States
CCTU

Recruiting

Pembrolizumab in Hepatocellular Carcinoma

HCC

Hong Kong
HUYABIO International, LLC.

Active, not recruiting

A Study of HBI-8000 (Tucidinostat) With Pembrolizumab in Non-Small Cell Lung Cancer (HBI-8000)

Non Small Cell Lung Cancer

United States
Prof. Dr. Matthias Preusser

Unknown

Study on Pembrolizumab for Recurrent Primary Central Nervous System Lymphoma (PCNSL)

Primary Central Nervous System Lymphoma

Austria
Sichuan University
Geneplus-Beijing Co. Ltd.

Recruiting

A Prospective Study of Constructing Immune Repertoire to Monitor the Therapeutic Effect in NSCLC Patients

Non-small Cell Lung Cancer

China
Chinese University of Hong Kong

Completed

Pembrolizumab in Advanced/Metastatic Acral Lentiginous Melanoma

Acral Lentiginous Melanoma

Hong Kong
Samsung Medical Center

Recruiting

Pembrolizumab for Metastatic NSCLC Patients Expressing PD-L1 Who Have Their Own PDX

Metastatic Non-Small Cell Lung Carcinoma

Korea, Republic of

Veliparib, Pembrolizumab, and Combination Chemotherapy in Treating Patient With Locally Advanced Rectal Cancer

A Phase II Clinical Trial Platform of Sensitization Utilizing Total Neoadjuvant Therapy (TNT) in Rectal Cancer

Study Overview

Status

Conditions

Intervention / Treatment

Detailed Description

Study Type

Enrollment (Actual)

Phase

Contacts and Locations

Study Locations

Participation Criteria

Eligibility Criteria

Ages Eligible for Study

Accepts Healthy Volunteers

Description

Study Plan

How is the study designed?

Design Details

Number of Arms

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Secondary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Other Outcome Measures

Outcome Measure

Measure Description

Time Frame

Collaborators and Investigators

Sponsor

Collaborators

Investigators

Publications and helpful links

General Publications

Study record dates

Study Major Dates

Study Start (Actual)

Primary Completion (Actual)

Study Completion (Actual)

Study Registration Dates

First Submitted

First Submitted That Met QC Criteria

First Posted (Estimated)

Study Record Updates

Last Update Posted (Actual)

Last Update Submitted That Met QC Criteria

Last Verified

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Clinical Trials on Rectal Adenocarcinoma

Clinical Trials on Pembrolizumab

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Conditions

Rare Diseases

Drug Interventions

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