Testing the Addition of an Anti-Cancer Drug, Irinotecan, to the Standard Chemotherapy Treatment (FOLFOX) After Long-Course Radiation Therapy for Advanced-Stage Rectal Cancers to Improve the Rate of Complete Response and Long-Term Rates of Organ Preservation

Locally Advanced Rectal Carcinoma Clinical Trial

— JANUS  

Official title:

The Janus Rectal Cancer Trial: A Randomized Phase II Trial Testing The Efficacy of Triplet Versus Doublet Chemotherapy to Achieve Clinical Complete Response in Patients With Locally Advanced Rectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05610163
• Other study ID #: A022104
• Secondary ID: NCI-2022-07800U1
• Status: Recruiting
• Phase: Phase 2
• Start date: December 8, 2022
• Est. completion date: September 2032

Study information

• Verified date: May 2024
• Source: Alliance for Clinical Trials in Oncology
• Contact: J. Joshua Smith, MD
• Phone: 212-639-5807
• Email: smithj5[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial compares the effect of irinotecan versus oxaliplatin after long-course chemoradiation in patients with stage II-III rectal cancer. Combination chemotherapy drugs, such as FOLFIRINOX (fluorouracil, irinotecan, leucovorin, and oxaliplatin), FOLFOX (leucovorin, fluorouracil, oxaliplatin, and irinotecan ), and CAPOX (capecitabin and oxaliplatin) 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. FOLFOX or CAPOX are used after chemoradiation as usual treatment for rectal cancer. Giving FOLFIRINOX after chemoradiation may increase the response rate and lead to higher rates of clinical complete response (with a chance of avoiding surgery) compared to FOLFOX or CAPOX after chemoradiation in patients with locally advanced rectal cancer.

Description:

PRIMARY OBJECTIVE:

I. To evaluate and compare the clinical complete response (cCR) rates in patients with locally advanced rectal cancer treated with neoadjuvant long-course neoadjuvant radiotherapy (LCRT) followed by neoadjuvant modified fluorouracil, irinotecan, leucovorin, and oxaliplatin (mFOLFIRINOX) versus neoadjuvant LCRT followed by neoadjuvant modified leucovorin , fluorouracil, and oxaliplatin (mFOLFOX6).

SECONDARY OBJECTIVES:

I. To evaluate and compare organ-preservation-time (OPT) between two treatment arms.

II. To evaluate and compare the disease-free survival (DFS) time between the two treatment arms.

III. To evaluate and compare time to distant metastasis between two treatment arms.

IV. To evaluate and compare overall survival (OS) between two treatment arms. V. To evaluate and compare toxicity profiles of total neoadjuvant therapy (TNT) between two treatment arms.

EXPLORATORY OBJECTIVE:

I. Evaluation of circulating tumor deoxyribonucleic acid (ctDNA) kinetics during neoadjuvant therapy & surveillance and to correlate with radiographic, pathologic, and clinical outcomes.

OUTLINE: Patients are randomized to 1 of 2 arms.

GROUP I: Patients receive long-course chemoradiation therapy on study and then receive either: FOLFOX regimen consisting of leucovorin intravenously (IV), fluorouracil IV, and oxaliplatin IV or CAPOX consisting of capecitabine orally (PO), and oxaliplatin IV on study. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), and biospecimen collection throughout the trial. Patients also undergo sigmoidoscopy throughout the trial and biopsy during screening.

GROUP II: Patients receive long-course chemoradiation therapy on study and then receive FOLFIRINOX regimen consisting of leucovorin IV, fluorouracil IV, irinotecan IV, and oxaliplatin IV on study. Patients undergo CT scan, MRI scan, and blood specimen collection throughout the trial. Patients undergo sigmoidoscopy throughout the trial and biopsy during screening.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 312
• Est. completion date: September 2032
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Stage: Clinical stage II or III rectal adenocarcinoma defined as T4N0 or any T with node positive disease (any T, N+); also T3N0 requiring abdominal perineal resection (APR) or coloanal anastomosis

• Tumor site: Rectum; =< 12cm from the anal verge

• No prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation therapy administered as treatment for colorectal cancer within the past 5 years is allowed

• Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects

• Therefore, for women of childbearing potential only, a negative pregnancy test (urine or serum according to institutional guidelines) done =< 14 days prior to registration is required. Female subjects agree to use highly effective contraception combined with an additional barrier method (e.g, diaphragm, with a spermicide) while on study and for >= 9 months after last dose of study drug, and the same criteria are applicable to male subjects if they have a partner of childbirth potential. Male subject agrees to use a condom and not donate sperm while in this study and for >= 6 months after the last treatment

• Age >= 18 years

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (or Karnofsky >= 60%)

• Absolute neutrophil count (ANC) >= 1,500/mm^3

• Platelet count >= 100,000/mm

• Creatinine =< 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance >= 50 mL/min

^3

• Total bilirubin =< 1.5 x upper limit of normal (ULN)

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN)

• No upper rectal tumors (distal margin of tumor > 12 cm from the anal verge)

• No recurrent rectal cancer; prior transanal excision, prior distal sigmoid cancer with a low anastomosis

• No known mismatch repair deficient rectal adenocarcinoma

• Human immunodeficiency virus HIV-infected patients on effective anti-retro viral therapy with undetectable viral load within 6 months are eligible for this trial

• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardio toxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification1. To be eligible for this trial, patients should be class 2B or better

• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study * Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment

Related Conditions & MeSH terms

• Locally Advanced Rectal Carcinoma
• Rectal Neoplasms
• Stage II Rectal Cancer AJCC v8
• Stage III Rectal Cancer AJCC v8

Intervention

Drug:
• Capecitabine
Given PO
• 5-fluorouracil
Given IV
• Leucovorin calcium
Given IV
• Irinotecan
Given IV
• Oxaliplatin
Given IV

Radiation:
• Long Course Chemoradiotherapy
Receive LCRT

Procedure:
• Computed Tomography
undergo CT
• Magnetic Resonance Imaging
undergo MRI
• Sigmoidoscopy
undergo sigmoidoscopy
• biopsy
undergo biopsy

Locations

Country	Name	City	State
Puerto Rico	Cancer Center-Metro Medical Center Bayamon	Bayamon
Puerto Rico	Doctors Cancer Center	Manati
Puerto Rico	Centro Comprensivo de Cancer de UPR	San Juan
Puerto Rico	San Juan City Hospital	San Juan
Puerto Rico	San Juan Community Oncology Group	San Juan
United States	Hawaii Cancer Care - Westridge	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Queen's Cancer Center - Pearlridge	'Aiea	Hawaii
United States	The Cancer Center of Hawaii-Pali Momi	'Aiea	Hawaii
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Atrium Health Stanly/LCI-Albemarle	Albemarle	North Carolina
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	AdventHealth Altamonte	Altamonte Springs	Florida
United States	UPMC Altoona	Altoona	Pennsylvania
United States	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Mission Cancer and Blood - Ankeny	Ankeny	Iowa
United States	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	PCR Oncology	Arroyo Grande	California
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	Northwest Wisconsin Cancer Center	Ashland	Wisconsin
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland
United States	MedStar Good Samaritan Hospital	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Advocate Good Shepherd Hospital	Barrington	Illinois
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Saint Charles Health System	Bend	Oregon
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Billings Clinic Cancer Center	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	OSF Saint Joseph Medical Center	Bloomington	Illinois
United States	Saint Elizabeth Boardman Hospital	Boardman	Ohio
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	Trinity Health Medical Center - Brighton	Brighton	Michigan
United States	University of Michigan - Brighton Center for Specialty Care	Brighton	Michigan
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	New York-Presbyterian/Brooklyn Methodist Hospital	Brooklyn	New York
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Minnesota Oncology - Burnsville	Burnsville	Minnesota
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	UPMC Camp Hill	Camp Hill	Pennsylvania
United States	Aultman Health Foundation	Canton	Ohio
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan
United States	Trinity Health Medical Center - Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Carlisle Regional Cancer Center	Carlisle	Pennsylvania
United States	Mercy Cancer Center - Carmichael	Carmichael	California
United States	Mercy San Juan Medical Center	Carmichael	California
United States	Caro Cancer Center	Caro	Michigan
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Duke Cancer Institute Cary	Cary	North Carolina
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Saint Mary's Hospital	Centralia	Illinois
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Atrium Health Pineville/LCI-Pineville	Charlotte	North Carolina
United States	Atrium Health University City/LCI-University	Charlotte	North Carolina
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Levine Cancer Institute-Ballantyne	Charlotte	North Carolina
United States	Levine Cancer Institute-SouthPark	Charlotte	North Carolina
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Morton Plant Hospital	Clearwater	Florida
United States	Wake Forest University at Clemmons	Clemmons	North Carolina
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Mission Cancer and Blood - West Des Moines	Clive	Iowa
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Baptist Memorial Hospital and Cancer Center-Collierville	Collierville	Tennessee
United States	Memorial Hospital North	Colorado Springs	Colorado
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Saint Francis Cancer Center	Colorado Springs	Colorado
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	Baptist Memorial Hospital and Cancer Center-Golden Triangle	Columbus	Mississippi
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Atrium Health Cabarrus/LCI-Concord	Concord	North Carolina
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	MD Anderson in The Woodlands	Conroe	Texas
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Ochsner Hematology Oncology North Shore - Covington (West Region)	Covington	Louisiana
United States	Greater Regional Medical Center	Creston	Iowa
United States	Northwest Cancer Center - Main Campus	Crown Point	Indiana
United States	AMG Crystal Lake - Oncology	Crystal Lake	Illinois
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern Simmons Cancer Center - RedBird	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Carle at The Riverfront	Danville	Illinois
United States	Dayton Physician LLC - Englewood	Dayton	Ohio
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Essentia Health - Deer River Clinic	Deer River	Minnesota
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Porter Adventist Hospital	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	UCHealth - Cherry Creek	Denver	Colorado
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Essentia Health Saint Mary's - Detroit Lakes Clinic	Detroit Lakes	Minnesota
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Advocate Good Samaritan Hospital	Downers Grove	Illinois
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Duke University Medical Center	Durham	North Carolina
United States	Northwest Oncology LLC	Dyer	Indiana
United States	Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Saint Elizabeth Healthcare Edgewood	Edgewood	Kentucky
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Advocate Sherman Hospital	Elgin	Illinois
United States	Mercy Cancer Center - Elk Grove	Elk Grove	California
United States	Elmhurst Memorial Hospital	Elmhurst	Illinois
United States	Saint Vincent Hospital	Erie	Pennsylvania
United States	UPMC Hillman Cancer Center Erie	Erie	Pennsylvania
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Inova Fair Oaks Hospital	Fairfax	Virginia
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Farmington Health Center	Farmington	Utah
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Beaumont Hospital - Farmington Hills	Farmington Hills	Michigan
United States	UPMC Cancer Center at UPMC Horizon	Farrell	Pennsylvania
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Orion Cancer Care	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	The New York Hospital Medical Center of Queens	Flushing	New York
United States	Levine Cancer Institute - Rutherford	Forest City	North Carolina
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	Saint Elizabeth Healthcare Fort Thomas	Fort Thomas	Kentucky
United States	Parkview Regional Medical Center	Fort Wayne	Indiana
United States	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas
United States	Essentia Health - Fosston	Fosston	Minnesota
United States	Dana-Farber Cancer Institute at Foxborough	Foxboro	Massachusetts
United States	Beebe South Coastal Health Campus	Frankford	Delaware
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Washington Hospital	Fremont	California
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Gibbs Cancer Center-Gaffney	Gaffney	South Carolina
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
United States	Levine Cancer Institute-Gaston	Gastonia	North Carolina
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Tidelands Georgetown Memorial Hospital	Georgetown	South Carolina
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	The West Clinic - Wolf River	Germantown	Tennessee
United States	Glens Falls Hospital	Glens Falls	New York
United States	SCL Health Cancer Centers of Colorado - Lutheran Medical Center	Golden	Colorado
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Northwell Health Cancer Institute at Huntington	Greenlawn	New York
United States	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	East Carolina University	Greenville	North Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Baptist Cancer Center-Grenada	Grenada	Mississippi
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan
United States	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Hartford Hospital	Hartford	Connecticut
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Essentia Health-Hayward Clinic	Hayward	Wisconsin
United States	Advocate South Suburban Hospital	Hazel Crest	Illinois
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	OptumCare Cancer Care at Seven Hills	Henderson	Nevada
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	UCHealth Highlands Ranch Hospital	Highlands Ranch	Colorado
United States	University of North Carolina-Hillsborough Campus	Hillsborough	North Carolina
United States	Northwest Cancer Center - Hobart	Hobart	Indiana
United States	Saint Mary Medical Center	Hobart	Indiana
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	Lyndon Baines Johnson General Hospital	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	MD Anderson West Houston	Houston	Texas
United States	IRMC Cancer Center	Indiana	Pennsylvania
United States	City of Hope at Irvine Lennar	Irvine	California
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Essentia Health - Jamestown Clinic	Jamestown	North Dakota
United States	MU Health Care Goldschmidt Cancer Center	Jefferson City	Missouri
United States	Jefferson Hospital	Jefferson Hills	Pennsylvania
United States	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Kingman Regional Medical Center	Kingman	Arizona
United States	FHCC at EvergreenHealth	Kirkland	Washington
United States	AdventHealth Kissimmee	Kissimmee	Florida
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Town Center	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	GenesisCare USA - Fort Apache	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	OptumCare Cancer Care at MountainView	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	MD Anderson League City	League City	Texas
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Inova Loudoun Hospital	Leesburg	Virginia
United States	Beebe Medical Center	Lewes	Delaware
United States	Saint Joseph Hospital	Lexington	Kentucky
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	AMG Libertyville - Oncology	Libertyville	Illinois
United States	Condell Memorial Hospital	Libertyville	Illinois
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Atrium Health Lincoln/LCI-Lincolnton	Lincolnton	North Carolina
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	The Dana-Farber Cancer Institute at Londonderry	Londonderry	New Hampshire
United States	Longmont United Hospital	Longmont	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Los Angeles General Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	Saint Joseph's Hospital-North	Lutz	Florida
United States	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Solinsky Center for Cancer Care	Manchester	New Hampshire
United States	North Shore University Hospital	Manhasset	New York
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Sovah Health Martinsville	Martinsville	Virginia
United States	Levine Cancer Institute - Union West	Matthews	North Carolina
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania
United States	UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion	Mechanicsburg	Pennsylvania
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	Froedtert Menomonee Falls Hospital	Menomonee Falls	Wisconsin
United States	Mercy Cancer Center	Merced	California
United States	Midstate Medical Center	Meriden	Connecticut
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Dana Farber-Merrimack Valley	Methuen	Massachusetts
United States	Garnet Health Medical Center	Middletown	New York
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Dana-Farber/Brigham and Women's Cancer Center at Milford Regional	Milford	Massachusetts
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	NYU Langone Hospital - Long Island	Mineola	New York
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Community Medical Center	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Atrium Health Union/LCI-Union	Monroe	North Carolina
United States	Forbes Hospital	Monroeville	Pennsylvania
United States	UPMC Cancer Center - Monroeville	Monroeville	Pennsylvania
United States	UPMC Hillman Cancer Center - Monroeville	Monroeville	Pennsylvania
United States	Monticello Cancer Center	Monticello	Minnesota
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	UPMC Hillman Cancer Center in Coraopolis	Moon	Pennsylvania
United States	Northern Westchester Hospital	Mount Kisco	New York
United States	UPMC Hillman Cancer Center - Part of Frick Hospital	Mount Pleasant	Pennsylvania
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Skagit Regional Health Cancer Care Center	Mount Vernon	Washington
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	The Community Hospital	Munster	Indiana
United States	Women's Diagnostic Center - Munster	Munster	Indiana
United States	MUSC Health Tidelands Health Radiation Therapy Center	Murrells Inlet	South Carolina
United States	Arnold Palmer Cancer Center Medical Oncology Norwin	N. Huntingdon	Pennsylvania
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Providence Queen of The Valley	Napa	California
United States	Edward Hospital/Cancer Center	Naperville	Illinois
United States	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	UPMC Cancer Center-Natrona Heights	Natrona Heights	Pennsylvania
United States	Baptist Memorial Hospital and Cancer Center-Union County	New Albany	Mississippi
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	UPMC Hillman Cancer Center - New Castle	New Castle	Pennsylvania
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Lenox Hill Hospital	New York	New York
United States	Manhattan Eye Ear and Throat Hospital	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	Mount Sinai West	New York	New York
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Ascension Providence Hospitals - Novi	Novi	Michigan
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	HSHS Saint Elizabeth's Hospital	O'Fallon	Illinois
United States	Drexel Town Square Health Center	Oak Creek	Wisconsin
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Saint Joseph Hospital - Orange	Orange	California
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	University of Chicago Medicine-Orland Park	Orland Park	Illinois
United States	AdventHealth East Orlando	Orlando	Florida
United States	AdventHealth Orlando	Orlando	Florida
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Upstate Cancer Center at Oswego	Oswego	New York
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Baptist Memorial Hospital and Cancer Center-Oxford	Oxford	Mississippi
United States	Advocate High Tech Medical Park	Palos Heights	Illinois
United States	The Valley Hospital - Luckow Pavilion	Paramus	New Jersey
United States	Essentia Health - Park Rapids	Park Rapids	Minnesota
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Parker Adventist Hospital	Parker	Colorado
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Jefferson Torresdale Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	Mayo Clinic Hospital in Arizona	Phoenix	Arizona
United States	Avera Cancer Institute at Pierre	Pierre	South Dakota
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Mercy Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Passavant Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Saint Clair Hospital Cancer Center	Pittsburgh	Pennsylvania
United States	UPMC-Saint Margaret	Pittsburgh	Pennsylvania
United States	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania
United States	Edward Hospital/Cancer Center?Plainfield	Plainfield	Illinois
United States	Michigan Healthcare Professionals Pontiac	Pontiac	Michigan
United States	Trinity Health Saint Joseph Mercy Oakland Hospital	Pontiac	Michigan
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Duke Raleigh Hospital	Raleigh	North Carolina
United States	Queens Cancer Center	Rego Park	New York
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Radiation Oncology Associates	Reno	Nevada
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Valley Medical Center	Renton	Washington
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	UT Southwestern Clinical Center at Richardson/Plano	Richardson	Texas
United States	Reid Health	Richmond	Indiana
United States	VCU Massey Cancer Center at Stony Point	Richmond	Virginia
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Valley Health System Ridgewood Campus	Ridgewood	New Jersey
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Levine Cancer Institute-Rock Hill	Rock Hill	South Carolina
United States	Rock Hill Radiation Therapy Center	Rock Hill	South Carolina
United States	Mercy Cancer Center - Rocklin	Rocklin	California
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Mercy Cancer Center - Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Saint Anthony's Hospital Cancer Care Center	Saint Petersburg	Florida
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Salinas Valley Memorial	Salinas	California
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	University of Utah Sugarhouse Health Center	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Essentia Health Sandstone	Sandstone	Minnesota
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Providence Medical Foundation - Santa Rosa	Santa Rosa	California
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	FHCC South Lake Union	Seattle	Washington
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania
United States	Sidney Kimmel Cancer Center Washington Township	Sewell	New Jersey
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Saint Vincent Hospital Cancer Center at Sheboygan	Sheboygan	Wisconsin
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Atrium Health Cleveland/LCI-Cleveland	Shelby	North Carolina
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Saint Michael Cancer Center	Silverdale	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Phelps Memorial Hospital Center	Sleepy Hollow	New York
United States	City of Hope South Pasadena	South Pasadena	California
United States	Dana-Farber/Brigham and Women's Cancer Center at South Shore	South Weymouth	Massachusetts
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Baptist Memorial Hospital and Cancer Center-Desoto	Southhaven	Mississippi
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Essentia Health-Spooner Clinic	Spooner	Wisconsin
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	MD Anderson in Sugar Land	Sugar Land	Texas
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	Essentia Health Saint Mary's Hospital - Superior	Superior	Wisconsin
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	SUNY Upstate Medical Center-Community Campus	Syracuse	New York
United States	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	Holy Name Hospital	Teaneck	New Jersey
United States	Scott and White Memorial Hospital	Temple	Texas
United States	City of Hope South Bay	Torrance	California
United States	Dayton Physicians LLC - Troy	Troy	Ohio
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	MGC Hematology Oncology-Union	Union	South Carolina
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	UPMC Cancer Center-Uniontown	Uniontown	Pennsylvania
United States	UPMC Uniontown Hospital Radiation Oncology	Uniontown	Pennsylvania
United States	City of Hope Upland	Upland	California
United States	Carle Cancer Center	Urbana	Illinois
United States	Northwest Cancer Center - Valparaiso	Valparaiso	Indiana
United States	Legacy Cancer Institute Medical Oncology and Day Treatment	Vancouver	Washington
United States	Legacy Salmon Creek Hospital	Vancouver	Washington
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Upstate Cancer Center at Verona	Verona	New York
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Saint Joseph Warren Hospital	Warren	Ohio
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	George Washington University Medical Center	Washington	District of Columbia
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	UPMC Cancer Center-Washington	Washington	Pennsylvania
United States	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Wilmot Cancer Institute at Webster	Webster	New York
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Froedtert West Bend Hospital/Kraemer Cancer Center	West Bend	Wisconsin
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan
United States	Chester County Hospital	West Chester	Pennsylvania
United States	Lexington Medical Center	West Columbia	South Carolina
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Reading Hospital	West Reading	Pennsylvania
United States	William E Kahlert Regional Cancer Center/Sinai Hospital	Westminster	Maryland
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Valley Health System-Hematology/Oncology	Westwood	New Jersey
United States	Wexford Health and Wellness Pavilion	Wexford	Pennsylvania
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Wake Forest Baptist Health - Wilkes Medical Center	Wilkesboro	North Carolina
United States	Divine Providence Hospital	Williamsport	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Asplundh Cancer Pavilion	Willow Grove	Pennsylvania
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Aspirus Cancer Care - Wisconsin Rapids	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Woodland Memorial Hospital	Woodland	California
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
United States	Avera Cancer Institute at Yankton	Yankton	South Dakota
United States	UPMC Memorial	York	Pennsylvania
United States	Saint Elizabeth Youngstown Hospital	Youngstown	Ohio
United States	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clincal Complete Response (cCR) Rates	efined as the number of patients who achieved cCR at the end of total neoadjuvant therapy (TNT) divided by number of patients included in the analysis population. This endpoint will be assessed within 8-12 weeks after completion of TNT. If there is a cCR, then the patient will be counted in the numerator. If there is a near-complete response (nCR) then a re-evaluation within 4-8 weeks will be performed. If the tumor has evolved to a cCR, then the patient will be counted in the numerator. Otherwise, the patient will be deemed as NOT achieving cCR status.; divided by number of patients included in the analysis population.	Up to 5 years
Secondary	Disease-free survival (DFS) rate	Defined as the time from date of randomization to the date of first occurrence of the following events: death due to all causes, tumor that recurs locally after an R0 total mesorectal excision (TME), tumor that regrows after an initial apparent clinical and radiological CR and cannot be surgically removed with an R0 TME, and M1 disease diagnosed at any point after the initiation of treatment.	rom date of randomization, assessed up to 5 years
Secondary	Organ-preservation-time (OPT)	Defined as time from the date of randomization to the date of the first occurrence of the following events: TME performed or attempted, tumor that regrows after an initial apparent clinical and radiological complete response (CR), and death due to all causes.	From date of randomization, assessed up to 5 years
Secondary	Time to distant metastasis (TDM)	Will be estimated, in each arm, using the method of Kaplan-Meier and compared by a stratified Cox regression model.	From the date of randomization to the date of first documented distant metastasis, assessed up to 5 years
Secondary	Overall survival (OS)	Will be estimated, in each arm, using the method of Kaplan-Meier and compared by a stratified Cox regression model.	From the date of randomization to the date of death due to all causes, assessed up to 5 years
Secondary	Incidence of adverse events (AEs)	Defined as the proportion of patients experienced at least one Grade 3, Grade 4, or Grade 5 of each type of AE. The overall adverse event rates for grade 3 or higher adverse events will be compared between two treatment groups using Chi-square test (or Fisher's exact test if the data in the contingency table is sparse).	Up to 5 years