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

Rectal Adenocarcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02921256
• Other study ID #: NCI-2016-00222
• Secondary ID: NCI-2016-00222NR
• Status: Completed
• Phase: Phase 2
• Start date: January 11, 2017
• Est. completion date: September 20, 2023

Study information

• Verified date: March 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 363
• Est. completion date: September 20, 2023
• Est. primary completion date: April 21, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Rectal Adenocarcinoma
• Rectal Neoplasms
• Stage II Rectal Cancer AJCC v7
• Stage III Rectal Cancer AJCC v7

Intervention

Drug:
• Capecitabine
Given PO
• Fluorouracil
Given IV

Radiation:
• Intensity-Modulated Radiation Therapy
Undergo intensity modulated radiation therapy

Drug:
• Leucovorin
Given IV
• Oxaliplatin
Given IV

Biological:
• Pembrolizumab
Given IV

Drug:
• Veliparib
Given PO

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	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	Avera Cancer Institute-Aberdeen	Aberdeen	South Dakota
United States	Jefferson Abington Hospital	Abington	Pennsylvania
United States	Hickman Cancer Center	Adrian	Michigan
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Atrium Health Stanly/LCI-Albemarle	Albemarle	North Carolina
United States	New Mexico Oncology Hematology Consultants	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	Northwest Community Hospital	Arlington Heights	Illinois
United States	PCR Oncology	Arroyo Grande	California
United States	Mission Hospital	Asheville	North Carolina
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	MultiCare Auburn Medical Center	Auburn	Washington
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	AIS Cancer Center at San Joaquin Community Hospital	Bakersfield	California
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Louisiana Hematology Oncology Associates LLC	Baton Rouge	Louisiana
United States	LSU Health Baton Rouge-North Clinic	Baton Rouge	Louisiana
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Our Lady of the Lake Physicians Group - Medical Oncology	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	McLaren Cancer Institute-Bay City	Bay City	Michigan
United States	Northwell Health Imbert Cancer Center	Bay Shore	New York
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	Overlake Medical Center	Bellevue	Washington
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
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	Saint Vincent Healthcare	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	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	United Hospital Center	Bridgeport	West Virginia
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	Crozer-Keystone Regional Cancer Center at Broomall	Broomall	Pennsylvania
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Mills-Peninsula Medical Center	Burlingame	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	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Cleveland Clinic Mercy Hospital	Canton	Ohio
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	SIH Cancer Institute	Carterville	Illinois
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Sandra L Maxwell Cancer Center	Cedar City	Utah
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	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	Geauga Hospital	Chardon	Ohio
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Charleston Division	Charleston	West Virginia
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	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	Memorial Hospital	Chattanooga	Tennessee
United States	Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Enloe Medical Center	Chico	California
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	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	McLaren Cancer Institute-Clarkston	Clarkston	Michigan
United States	Case Western Reserve University	Cleveland	Ohio
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Baptist Memorial Hospital and Cancer Center-Collierville	Collierville	Tennessee
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Atrium Health Cabarrus/LCI-Concord	Concord	North Carolina
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	City of Hope Corona	Corona	California
United States	Mary Bird Perkins Cancer Center - Covington	Covington	Louisiana
United States	Northshore Oncology Associates-Covington	Covington	Louisiana
United States	Baylor University Medical Center	Dallas	Texas
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Carle at The Riverfront	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Genesis Cancer Care Institute	Davenport	Iowa
United States	Genesis Medical Center - East Campus	Davenport	Iowa
United States	Iowa Cancer Specialists	Davenport	Iowa
United States	Dayton Physician LLC-Miami Valley Hospital North	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	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	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mercy Medical Center - 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	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Essentia Health Saint Mary's - Detroit Lakes Clinic	Detroit Lakes	Minnesota
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Kaiser Permanente Dublin	Dublin	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	Saint Luke's Hospital of Duluth	Duluth	Minnesota
United States	Northeast Radiation Oncology Center	Dunmore	Pennsylvania
United States	Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
United States	Swedish Medical Center	Englewood	Colorado
United States	Saint Vincent Hospital	Erie	Pennsylvania
United States	Deaconess Clinic Downtown	Evansville	Indiana
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
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	Beaumont Hospital - Farmington Hills	Farmington Hills	Michigan
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Virginia Mason Federal Way Medical Center	Federal Way	Washington
United States	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota
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	McLaren Cancer Institute-Flint	Flint	Michigan
United States	Singh and Arora Hematology Oncology PC	Flint	Michigan
United States	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	Parkview Hospital Randallia	Fort Wayne	Indiana
United States	Parkview Regional Medical Center	Fort Wayne	Indiana
United States	Essentia Health - Fosston	Fosston	Minnesota
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Fresno Cancer Center	Fresno	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Unity Hospital	Fridley	Minnesota
United States	Gibbs Cancer Center-Gaffney	Gaffney	South Carolina
United States	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	University of Texas Medical Branch	Galveston	Texas
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	The West Clinic - Wolf River	Germantown	Tennessee
United States	MultiCare Gig Harbor Medical Park	Gig Harbor	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Gig Harbor	Gig Harbor	Washington
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Crozer Regional Cancer Center at Brinton Lake	Glen Mills	Pennsylvania
United States	Glens Falls Hospital	Glens Falls	New York
United States	Goshen Center for Cancer Care	Goshen	Indiana
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
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	Smilow Cancer Hospital Care Center - Guilford	Guilford	Connecticut
United States	Sentara Cancer Institute at Sentara CarePlex Hospital	Hampton	Virginia
United States	Hartford Hospital	Hartford	Connecticut
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	OptumCare Cancer Care at Seven Hills	Henderson	Nevada
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii
United States	Island Urology	Honolulu	Hawaii
United States	Kaiser Permanente Moanalua Medical Center	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 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	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Mary Bird Perkins Cancer Center - Houma	Houma	Louisiana
United States	Oncology Center of The South Incorporated	Houma	Louisiana
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Novant Health Presbyterian Medical Center Huntersville	Huntersville	North Carolina
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Allegiance Health	Jackson	Michigan
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Essentia Health - Jamestown Clinic	Jamestown	North Dakota
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Jefferson Hospital	Jefferson Hills	Pennsylvania
United States	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin
United States	NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro	Jonesboro	Arkansas
United States	Freeman Health System	Joplin	Missouri
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Research Medical Center	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Tri-Cities Cancer Center	Kennewick	Washington
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	Seattle Cancer Care Alliance at EvergreenHealth	Kirkland	Washington
United States	UC San Diego Moores Cancer Center	La Jolla	California
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	City of Hope Antelope Valley	Lancaster	California
United States	Karmanos Cancer Institute at McLaren Greater Lansing	Lansing	Michigan
United States	Sparrow Hospital	Lansing	Michigan
United States	McLaren Cancer Institute-Lapeer Region	Lapeer	Michigan
United States	Comprehensive Cancer Centers of Nevada	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	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	UTMB Cancer Center at Victory Lakes	League City	Texas
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Beebe Medical Center	Lewes	Delaware
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Nebraska Cancer Research Center	Lincoln	Nebraska
United States	Nebraska Hematology and Oncology	Lincoln	Nebraska
United States	Southeast Nebraska Cancer Center - 68th Street Place	Lincoln	Nebraska
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Logan Regional Hospital	Logan	Utah
United States	Longmont United Hospital	Longmont	Colorado
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Jewish Hospital	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	McKee Medical Center	Loveland	Colorado
United States	Covenant Medical Center-Lakeside	Lubbock	Texas
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
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	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	Matthews Radiation Oncology Center	Matthews	North Carolina
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	The West Clinic - Mid-Town	Memphis	Tennessee
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	Froedtert Menomonee Falls Hospital	Menomonee Falls	Wisconsin
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Midstate Medical Center	Meriden	Connecticut
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Woodland Cancer Care Center	Michigan City	Indiana
United States	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio
United States	Garnet Health Medical Center	Middletown	New York
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	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	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana
United States	Community Medical Hospital	Missoula	Montana
United States	Southern Cancer Center PC-Mobile	Mobile	Alabama
United States	Southern Cancer Center PC-Providence	Mobile	Alabama
United States	Southern Cancer Center PC-Springhill	Mobile	Alabama
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	Kaiser Permanente-Modesto	Modesto	California
United States	Memorial Medical Center	Modesto	California
United States	Atrium Health Union/LCI-Union	Monroe	North Carolina
United States	Forbes Hospital	Monroeville	Pennsylvania
United States	Monticello Cancer Center	Monticello	Minnesota
United States	Virtua Samson Cancer Center	Moorestown	New Jersey
United States	Franciscan Health Mooresville	Mooresville	Indiana
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	McLaren Cancer Institute-Macomb	Mount Clemens	Michigan
United States	Virtua Memorial	Mount Holly	New Jersey
United States	McLaren Cancer Institute-Central Michigan	Mount Pleasant	Michigan
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Skagit Regional Health Cancer Care Center	Mount Vernon	Washington
United States	Skagit Valley Hospital	Mount Vernon	Washington
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Intermountain Medical Center	Murray	Utah
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
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	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut
United States	Yale University	New Haven	Connecticut
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	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	Chancellor Center for Oncology	Newburgh	Indiana
United States	Lakeland Hospital Niles	Niles	Michigan
United States	Sentara Leigh Hospital	Norfolk	Virginia
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut
United States	William Backus Hospital	Norwich	Connecticut
United States	Sutter Cancer Research Consortium	Novato	California
United States	Ascension Providence Hospitals - Novi	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Kaiser Permanente Oakland-Broadway	Oakland	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	Integris Cancer Institute of Oklahoma	Oklahoma City	Oklahoma
United States	Integris Southwest Medical Center	Oklahoma City	Oklahoma
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Olathe Health Cancer Center	Olathe	Kansas
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	Nebraska Cancer Specialists - Omaha	Omaha	Nebraska
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	McLaren Cancer Institute-Owosso	Owosso	Michigan
United States	Baptist Memorial Hospital and Cancer Center-Oxford	Oxford	Mississippi
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Essentia Health - Park Rapids	Park Rapids	Minnesota
United States	Camden Clark Medical Center	Parkersburg	West Virginia
United States	University Hospitals Parma Medical Center	Parma	Ohio
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	McLaren Cancer Institute-Northern Michigan	Petoskey	Michigan
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Ascension Via Christi - Pittsburg	Pittsburg	Kansas
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Berkshire Medical Center - Cancer Center	Pittsfield	Massachusetts
United States	21st Century Oncology-Pontiac	Pontiac	Michigan
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	McLaren-Port Huron	Port Huron	Michigan
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Puyallup	Puyallup	Washington
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	UNC Rex Healthcare	Raleigh	North Carolina
United States	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California
United States	University Hospitals Portage Medical Center	Ravenna	Ohio
United States	Kaiser Permanente-Redwood City	Redwood City	California
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
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	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Reid Health	Richmond	Indiana
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Kaiser Permanente-Riverside	Riverside	California
United States	Riverton Hospital	Riverton	Utah
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	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois
United States	Rohnert Park Cancer Center	Rohnert Park	California
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Kaiser Permanente-Roseville	Roseville	California
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	Sutter Roseville Medical Center	Roseville	California
United States	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Kaiser Permanente - Sacramento	Sacramento	California
United States	Kaiser Permanente Downtown Commons	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	South Sacramento Cancer Center	Sacramento	California
United States	Sutter Medical 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	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Saint George Regional Medical Center	Saint George	Utah
United States	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
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	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Salina Regional Health Center	Salina	Kansas
United States	TidalHealth Peninsula Regional	Salisbury	Maryland
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	Kaiser Permanente-San Diego Zion	San Diego	California
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	Kaiser Permanente-San Rafael	San Rafael	California
United States	Kaiser San Rafael-Gallinas	San Rafael	California
United States	Essentia Health Sandstone	Sandstone	Minnesota
United States	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Christus Saint Vincent Regional Cancer Center	Santa Fe	New Mexico
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Regional West Medical Center Cancer Center	Scottsbluff	Nebraska
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware
United States	FHCC at Northwest Hospital	Seattle	Washington
United States	FHCC South Lake Union	Seattle	Washington
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Geisinger Medical Oncology-Selinsgrove	Selinsgrove	Pennsylvania
United States	Grand View Hospital	Sellersville	Pennsylvania
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Atrium Health Cleveland/LCI-Cleveland	Shelby	North Carolina
United States	Genesis Cancer Center - Silvis	Silvis	Illinois
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	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	City of Hope South Pasadena	South Pasadena	California
United States	Kaiser Permanente Cancer Treatment Center	South San Francisco	California
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
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	Spokane Valley Cancer Center-Mayfair	Spokane	Washington
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois
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	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Staten Island University Hospital	Staten Island	New York
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	Southwest Illinois Health Services LLP	Swansea	Illinois
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Saint Joe's	Tacoma	Washington
United States	Holy Name Hospital	Teaneck	New Jersey
United States	Scott and White Memorial Hospital	Temple	Texas
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	Dayton Physicians LLC - Troy	Troy	Ohio
United States	Upper Valley Medical Center	Troy	Ohio
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	University of Arizona Cancer Center-Orange Grove Campus	Tucson	Arizona
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	MGC Hematology Oncology-Union	Union	South Carolina
United States	City of Hope Upland	Upland	California
United States	Carle Cancer Center	Urbana	Illinois
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	Legacy Salmon Creek Hospital	Vancouver	Washington
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	Virtua Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	University Hospitals Sharon Health Center	Wadsworth	Ohio
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Smilow Cancer Hospital Care Center - Waterford	Waterford	Connecticut
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington
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	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Reading Hospital	West Reading	Pennsylvania
United States	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia
United States	Presbyterian Intercommunity Hospital	Whittier	California
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Asplundh Cancer Pavilion	Willow Grove	Pennsylvania
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	University of Michigan Health - West	Wyoming	Michigan
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of Patients Who Have a Tumor Resection Overall (and Conditional on Beginning Induction Chemotherapy, and Conditional on Beginning Chemoradiotherapy)	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	Time From Initiation of Chemoradiotherapy to Surgery in the Subset of Patients With Tumor Resection	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
Other	Rate of Disease Progression During Chemotherapy (Prior to Chemoradiation)	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	Rate of Clinical Complete Response Rate, ycT0	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	Rate of Negative Circumferential Margin	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	Rate of Completion of All Cycles of Neoadjuvant Chemotherapy	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	Rate of Completion of Full Course of Chemoradiation	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	Incidence of Toxicity Including Patient-reported Toxicities	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
Other	Correlative Molecular Predictors of Response and Distant Failure	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
Other	Relationship Between Radiographic Findings and Pathologic Outcomes	Will explore the relationship between radiographic findings and pathologic outcomes.	Up to 3 years
Primary	Neoadjuvant Rectal Cancer (NAR) Score	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	Overall Survival	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
Secondary	Disease Free Survival	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
Secondary	Rate of Pathologic Complete Response (Nodes and Tumor) ypT0 and ypN0	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
Secondary	Rate of Sphincter Preservation	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