Nivolumab and Ipilimumab in Treating Patients With Esophageal and Gastroesophageal Junction Adenocarcinoma Undergoing Surgery

Gastroesophageal Junction Adenocarcinoma Clinical Trial

Official title:

A Phase II/III Study of Peri-Operative Nivolumab and Ipilimumab in Patients With Locoregional Esophageal and Gastroesophageal Junction Adenocarcinoma

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT03604991
• Other study ID #: NCI-2018-01575
• Secondary ID: NCI-2018-01575EA
• Status: Suspended
• Phase: Phase 2/Phase 3
• Start date: May 3, 2019
• Est. completion date: January 31, 2026

Study information

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

Clinical Trial Summary

This phase II/III trial studies the usefulness of treatment with nivolumab and ipilimumab in addition to standard of care chemotherapy and radiation therapy in patients with esophageal and gastroesophageal junction adenocarcinoma who are undergoing surgery. Immunotherapy with antibodies, such as nivolumab and ipilimumab, may remove the brake on the body's immune system and may interfere with the ability of tumor cells to grow and spread. Chemotherapy and radiation therapy may reduce the tumor size and the amount of normal tissue that needs to be removed during surgery. A combined treatment with nivolumab and ipilimumab, chemotherapy, and radiation therapy might be more effective in patients with esophageal and gastroesophageal junction adenocarcinoma who are undergoing surgery.

Description:

PRIMARY OBJECTIVES:

I. To assess the pathologic complete response (pathCR) rate following administration of neoadjuvant carboplatin, paclitaxel and radiation therapy versus neoadjuvant carboplatin, paclitaxel, radiation therapy and nivolumab in patients with a resected locoregionally advanced esophageal or gastroesophageal junction adenocarcinoma.

II. To assess the disease-free survival (DFS) following administration of adjuvant nivolumab and ipilimumab versus adjuvant nivolumab in patients with a resected locoregionally advanced esophageal or gastroesophageal junction adenocarcinoma who received neoadjuvant treatment with carboplatin, paclitaxel and radiation therapy with or without nivolumab.

SECONDARY OBJECTIVES:

I. To assess the overall survival (OS) following administration of adjuvant nivolumab and ipilimumab versus nivolumab in patients with a resected locoregional esophageal or gastroesophageal junctional adenocarcinoma who received neoadjuvant treatment with carboplatin, paclitaxel and radiation therapy with or without nivolumab.

II. To assess the disease free survival (DFS) following administration of neoadjuvant carboplatin, paclitaxel, and radiation therapy with or without nivolumab in patients with a locoregional esophageal or gastroesophageal junction adenocarcinoma.

III. To assess the toxicity associated with the administration of neoadjuvant nivolumab in combination with carboplatin, paclitaxel and radiation therapy in patients with a locoregional esophageal or gastroesophageal junction adenocarcinoma.

IV. To assess the toxicity associated with the administration of adjuvant nivolumab and ipilimumab versus adjuvant nivolumab in patients with a resected locoregional esophageal or gastroesophageal junction adenocarcinoma who received neoadjuvant treatment with carboplatin, paclitaxel and radiation therapy with or without nivolumab.

OUTLINE:

STEP I: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive carboplatin intravenously (IV) and paclitaxel IV once weekly and undergo radiation therapy once daily (QD) (Monday-Friday) beginning on day 1 of each cycle. Cycles repeat every week for up to 5 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo a computed tomography (CT) or positron emission tomography (PET) scan during screening and follow-up and undergo collection of blood samples throughout the trial.

ARM B: Patients receive carboplatin, paclitaxel, and radiation therapy as in Arm A. Patients also receive nivolumab IV over 30 minutes on days 1 and 15 of each cycle. Cycles repeat every week for up to 5 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or PET scan during screening and follow-up and undergo collection of blood samples throughout the trial.

STEP II: Patients are randomized to 1 of 2 arms following standard of care surgery.

ARM C: Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 4 weeks for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and collection of blood samples throughout the trial.

ARM D: Patients receive nivolumab as in Arm C and receive ipilimumab IV over 90 minutes on day 1 of cycles 1 and 4 and day 15 of cycles 2 and 5. Treatment repeats every 4 weeks for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and collection of blood samples throughout the trial.

After completion of study treatment, patients are followed up every 3 months for 2 years, and then every 6 months for up to 5 years.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 278
• Est. completion date: January 31, 2026
• Est. primary completion date: January 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• STEP 1 RANDOMIZATION: Patients must be age >= 18 years

• STEP 1 RANDOMIZATION: Patients must have histologically confirmed T1N1-3M0 or T2-3N0-2M0 esophageal or gastroesophageal junctional adenocarcinoma (Siewert I and II)

• STEP 1 RANDOMIZATION: Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• STEP 1 RANDOMIZATION: Patents must be deemed a surgical candidate by a thoracic surgeon, surgical oncologist, or surgeon who is qualified to perform an esophagectomy

• STEP 1 RANDOMIZATION: Absolute neutrophil count >= 1,500/mcL (within less than or equal to 14 days prior to randomization)

• STEP 1 RANDOMIZATION: Platelets >= 100,000/mcL (within less than or equal to 14 days prior to randomization)

• STEP 1 RANDOMIZATION: Total bilirubin =< institutional upper limit of normal (ULN) (within less than or equal to 14 days prior to randomization)

• STEP 1 RANDOMIZATION: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (within less than or equal to 14 days prior to randomization)

• STEP 1 RANDOMIZATION: Serum creatinine =< 1.5 x institutional ULN (within less than or equal to 14 days prior to randomization)

• STEP 1 RANDOMIZATION: Hemoglobin (Hgb) >= 9 g/dL (within less than or equal to 14 days prior to randomization)

• STEP 1 RANDOMIZATION: Leukocytes >= 3,000/mm^3 (within less than or equal to 14 days prior to randomization)

• STEP 1 RANDOMIZATION: Patients may not have received prior chemotherapy or radiation therapy for management for this malignancy

• STEP 1 RANDOMIZATION: Patients may not have received prior immunotherapy for management of this malignancy or for any other past malignancy

• STEP 1 RANDOMIZATION: Patients must have no contraindication to receiving either carboplatin or paclitaxel chemotherapy

• STEP 1 RANDOMIZATION: Patients must have no contraindication to receiving radiation therapy

• STEP 1 RANDOMIZATION: Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, must be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue disease, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome must be excluded because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies must be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible

• STEP 1 RANDOMIZATION: Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)

• STEP 1 RANDOMIZATION: Patient must NOT have previous or concurrent malignancy. Exceptions are made for patients who meet any of the following conditions:

• Non-melanoma skin cancer, in situ cervical cancer, superficial bladder cancer, or breast cancer in situ OR

• Prior malignancy completely excised or removed and patient has been continuously disease free for > 5 years OR

• Date of last evidence of disease

• STEP 1 RANDOMIZATION: Patients must not have a condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses =< 10 mg/day prednisone equivalents are permitted in the absence of active autoimmune disease

• STEP 1 RANDOMIZATION: Patients must have adequate cardiac function including electrocardiogram (EKG) and echocardiogram for any patient with a history of congestive heart failure (CHF) or at risk because of underlying cardiovascular disease or exposure to cardiotoxic drugs

• STEP 1 RANDOMIZATION: For patients with evidence of uncontrolled CHF, myocardial infarction (MI), cardiomyopathy, or myositis, require a cardiac evaluation and clearance including lab tests and cardiology consultation (EKG, creatinine phosphokinase [CPK], troponin, and echocardiogram)

• STEP 1 RANDOMIZATION: Patients must not have a positive test result for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection. Testing should be conducted to determine eligibility

• STEP 1 RANDOMIZATION: Patients with a known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) must have no detectable viral load on a stable anti-viral regimen

• STEP 1 RANDOMIZATION: Patients must not be receiving any other investigational agents

• STEP 1 RANDOMIZATION: Patients with an uncontrolled intercurrent illness such as ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements will be excluded

• STEP 1 RANDOMIZATION: Patients must not be pregnant or breast-feeding due to potential harm to an unborn fetus and possible risk for adverse events in nursing infants from carboplatin, paclitaxel, ipilimumab or nivolumab

• All patients of childbearing potential must have a blood test or urine study done within 2 weeks prior to randomization to rule out pregnancy. Those enrolled on Arm B with nivolumab must agree to have a pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours of starting nivolumab to rule out pregnancy

• A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• STEP 1 RANDOMIZATION: Patients of childbearing potential must not expect to conceive children by either abstaining from sexual intercourse for the duration of their participation in the study or by agreeing to use both double barrier contraception and birth control pills or implants for at least one month prior to the start of the study drug and continuing for 5 months after the last dose of study drug. Investigators shall counsel patients of childbearing potential on the importance of pregnancy prevention and the implications of an unexpected pregnancy

• STEP 2 RANDOMIZATION: Patient registration must not exceed 12 weeks from time of esophagectomy

• STEP 2 RANDOMIZATION: Patients must have a post-operative ECOG performance status of 0-2

• STEP 2 RANDOMIZATION: Absolute neutrophil count >= 1,500/mcL (within less than or equal to 14 days prior to randomization)

• STEP 2 RANDOMIZATION: Platelets >= 100,000/mcL (within less than or equal to 14 days prior to randomization)

• STEP 2 RANDOMIZATION: Total bilirubin =< institutional upper limit of normal (ULN) (within less than or equal to 14 days prior to randomization)

• STEP 2 RANDOMIZATION: AST (SGOT)/ ALT (SGPT) =< 2.5 x institutional ULN (within less than or equal to 14 days prior to randomization)

• STEP 2 RANDOMIZATION: Serum creatinine =< 1.5 x institutional ULN (within less than or equal to 14 days prior to randomization)

• STEP 2 RANDOMIZATION: Patients must be disease free following esophagectomy as is demonstrated by having no evidence of disease on a post-surgical CT scan. Patients must also have a negative surgical margin (R0 resection)

• STEP 2 RANDOMIZATION: Patients must not have an active, known or suspected autoimmune disease or a condition requiring treatment with steroids or immunosuppressive agents. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger

• STEP 2 RANDOMIZATION: Patients must not have a condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone equivalents) or other immunosuppressive medications with 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg/day prednisone equivalents are permitted in the absence of active autoimmune disease

• STEP 2 RANDOMIZATION: Patients must not be receiving any other investigational agents

• STEP 2 RANDOMIZATION: Patients with an uncontrolled intercurrent illness such as ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements will be excluded

• STEP 2 RANDOMIZATION: Patients must not be pregnant or breast-feeding due to potential harm to an unborn fetus and possible risks for adverse events in nursing infants from nivolumab or ipilimumab

• All patients of childbearing potential must have a blood test or urine study done (minimum sensitivity 25 IU/L or equivalent units of HCG) within 2 weeks prior to randomization to rule out pregnancy. All patients must also agree to have a pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours of starting nivolumab to rule out pregnancy. Those enrolled on Arm D with ipilimumab must agree to have pregnancy tests within 72 hours of each ipilimumab administration to rule out pregnancy

• STEP 2 RANDOMIZATION: Patients of childbearing potential must not expect to conceive children by either abstaining from sexual intercourse for the duration of their participation in the study or by agreeing to use both double barrier contraception and birth control pills or implants for at least one month prior to the start of the study drug and continuing for 5 months after the last dose of study drug. Investigators shall counsel patients of childbearing potential on the importance of pregnancy prevention and the implications of an unexpected pregnancy

Related Conditions & MeSH terms

• Adenocarcinoma
• Clinical Stage II Esophageal Adenocarcinoma AJCC v8
• Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8
• Clinical Stage III Esophageal Adenocarcinoma AJCC v8
• Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8
• Clinical Stage IVA Esophageal Adenocarcinoma AJCC v8
• Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8
• Esophageal Adenocarcinoma
• Esophageal Neoplasms
• Gastroesophageal Junction Adenocarcinoma

Intervention

Procedure:
• Biospecimen Collection
Undergo collection of blood sample

Drug:
• Carboplatin
Given IV

Procedure:
• Computed Tomography
Undergo CT scan

Biological:
• Ipilimumab
Given IV
• Nivolumab
Given IV

Drug:
• Paclitaxel
Given IV

Procedure:
• Positron Emission Tomography
Undergo PET scan

Radiation:
• Radiation Therapy
Undergo radiation therapy

Locations

Country	Name	City	State
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	Lovelace Medical Center-Saint Joseph Square	Albuquerque	New Mexico
United States	New Mexico Oncology Hematology Consultants	Albuquerque	New Mexico
United States	Presbyterian Kaseman Hospital	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	Saint Luke's Cancer Center - Allentown	Allentown	Pennsylvania
United States	AdventHealth Altamonte	Altamonte Springs	Florida
United States	UPMC Altoona	Altoona	Pennsylvania
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	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	ThedaCare Regional Cancer Center	Appleton	Wisconsin
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 Proton Therapy Center	Atlanta	Georgia
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	Mount Sinai Comprehensive Cancer Center at Aventura	Aventura	Florida
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Eastern Maine Medical Center	Bangor	Maine
United States	MaineHealth Coastal Cancer Treatment Center	Bath	Maine
United States	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	Nebraska Medicine-Bellevue	Bellevue	Nebraska
United States	Overlake Medical Center	Bellevue	Washington
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	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford	Biddeford	Maine
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Elizabeth Boardman Hospital	Boardman	Ohio
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Boston Medical Center	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	Ocean University Medical Center	Brick	New Jersey
United States	United Hospital Center	Bridgeport	West Virginia
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	Trinity Health Medical Center - Brighton	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	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
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	Minnesota Oncology - Burnsville	Burnsville	Minnesota
United States	UPMC Hillman Cancer Center at Butler Health System	Butler	Pennsylvania
United States	UPMC Camp Hill	Camp Hill	Pennsylvania
United States	Sands Cancer Center	Canandaigua	New York
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	IU Health North Hospital	Carmel	Indiana
United States	Caro Cancer Center	Caro	Michigan
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
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	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Chelsea Hospital	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Northwestern University	Chicago	Illinois
United States	University of Illinois	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	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Mission Cancer and Blood - West Des Moines	Clive	Iowa
United States	Community Cancer Institute	Clovis	California
United States	University Oncology Associates	Clovis	California
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	Saint Francis Cancer Center	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	Mercy Hospital	Coon Rapids	Minnesota
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Greater Regional Medical Center	Creston	Iowa
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Noyes Memorial Hospital/Myers Cancer Center	Dansville	New York
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton Physician LLC - Englewood	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
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	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	Essentia Health Saint Mary's - Detroit Lakes Clinic	Detroit Lakes	Minnesota
United States	Illinois CancerCare-Dixon	Dixon	Illinois
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	Rhode Island Hospital at East Greenwich	East Greenwich	Rhode Island
United States	Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Saint Luke's Hospital-Anderson Campus	Easton	Pennsylvania
United States	HSHS Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Crossroads Cancer Center	Effingham	Illinois
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	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	Parkland Health Center - Farmington	Farmington	Missouri
United States	UPMC Cancer Center at UPMC Horizon	Farrell	Pennsylvania
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	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Regional Cancer Center-Lee Memorial Health System	Fort Myers	Florida
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas
United States	Essentia Health - Fosston	Fosston	Minnesota
United States	Beebe South Coastal Health Campus	Frankford	Delaware
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
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	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Glens Falls Hospital	Glens Falls	New York
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	Nebraska Cancer Specialists/Oncology Hematology West PC	Grand Island	Nebraska
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Bellin Memorial Hospital	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	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Baptist Cancer Center-Grenada	Grenada	Mississippi
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	Essentia Health-Hayward Clinic	Hayward	Wisconsin
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	Edward Hines Jr VA Hospital	Hines	Illinois
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	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	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Novant Health Cancer Institute - Huntersville	Huntersville	North Carolina
United States	Novant Health Presbyterian Medical Center Huntersville	Huntersville	North Carolina
United States	Cleveland Clinic Cancer Center Independence	Independence	Ohio
United States	IRMC Cancer Center	Indiana	Pennsylvania
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
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	University of Wisconsin Carbone Cancer Center - Johnson Creek	Johnson Creek	Wisconsin
United States	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania
United States	NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro	Jonesboro	Arkansas
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Ochsner Medical Center Kenner	Kenner	Louisiana
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Novant Health Cancer Institute - Kernersville	Kernersville	North Carolina
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	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 - 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	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Beebe Medical Center	Lewes	Delaware
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
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	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Monmouth Medical Center	Long Branch	New Jersey
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	Jewish Hospital	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	Lowell General Hospital	Lowell	Massachusetts
United States	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	University of Wisconsin Carbone Cancer Center - University Hospital	Madison	Wisconsin
United States	Southern Ocean County Medical Center	Manahawkin	New Jersey
United States	Cleveland Clinic Cancer Center Mansfield	Mansfield	Ohio
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	Matthews Radiation Oncology Center	Matthews	North Carolina
United States	Novant Health Cancer Institute - Matthews	Matthews	North Carolina
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Mount Sinai Medical Center	Miami Beach	Florida
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	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	Saint Patrick Hospital - Community Hospital	Missoula	Montana
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	UPMC Hillman Cancer Center in Coraopolis	Moon	Pennsylvania
United States	Novant Health Cancer Institute - Mooresville	Mooresville	North Carolina
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Novant Health Cancer Institute - Mount Airy	Mount Airy	North Carolina
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	Arnold Palmer Cancer Center Medical Oncology Norwin	N. Huntingdon	Pennsylvania
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Allegheny Valley Hospital	Natrona Heights	Pennsylvania
United States	Jersey Shore Medical Center	Neptune	New Jersey
United States	Baptist Memorial Hospital and Cancer Center-Union County	New Albany	Mississippi
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	UPMC Hillman Cancer Center - New Castle	New Castle	Pennsylvania
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	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	Newport Hospital	Newport	Rhode Island
United States	Ascension Providence Hospitals - Novi	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Mercy Hospital Oklahoma City	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	Nebraska Medicine-Village Pointe	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	AdventHealth East Orlando	Orlando	Florida
United States	AdventHealth Orlando	Orlando	Florida
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Baptist Memorial Hospital and Cancer Center-Oxford	Oxford	Mississippi
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	VA Palo Alto Health Care System	Palo Alto	California
United States	Essentia Health - Park Rapids	Park Rapids	Minnesota
United States	Parker Adventist Hospital	Parker	Colorado
United States	Camden Clark Medical Center	Parkersburg	West Virginia
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin	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	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
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-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	West Penn Hospital	Pittsburgh	Pennsylvania
United States	Michigan Healthcare Professionals Pontiac	Pontiac	Michigan
United States	Trinity Health Saint Joseph Mercy Oakland Hospital	Pontiac	Michigan
United States	Maine Medical Center-Bramhall Campus	Portland	Maine
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Pottstown Hospital	Pottstown	Pennsylvania
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Riverview Medical Center/Booker Cancer Center	Red Bank	New Jersey
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	UT Southwestern Clinical Center at Richardson/Plano	Richardson	Texas
United States	Reid Health	Richmond	Indiana
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Presbyterian Rust Medical Center/Jorgensen Cancer Center	Rio Rancho	New Mexico
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	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
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	Saint Helena Hospital	Saint Helena	California
United States	Dartmouth Cancer Center - North	Saint Johnsbury	Vermont
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	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	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	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Rowan Regional Medical Center	Salisbury	North Carolina
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	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Essentia Health Sandstone	Sandstone	Minnesota
United States	North Coast Cancer Care	Sandusky	Ohio
United States	MaineHealth Cancer Care Center of York County	Sanford	Maine
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford	Sanford	Maine
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Maine Medical Center- Scarborough Campus	Scarborough	Maine
United States	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
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	VCU Community Memorial Health Center	South Hill	Virginia
United States	Maine Medical Partners - South Portland	South Portland	Maine
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Baptist Memorial Hospital and Cancer Center-Desoto	Southhaven	Mississippi
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	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Novant Health Cancer Institute - Statesville	Statesville	North Carolina
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio
United States	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin
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	ProMedica Flower Hospital	Sylvania	Ohio
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	Novant Health Cancer Institute - Thomasville	Thomasville	North Carolina
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	Community Medical Center	Toms River	New Jersey
United States	Dayton Physicians LLC - Troy	Troy	Ohio
United States	Upper Valley Medical Center	Troy	Ohio
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	UPMC Cancer Center-Uniontown	Uniontown	Pennsylvania
United States	UPMC Uniontown Hospital Radiation Oncology	Uniontown	Pennsylvania
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
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	South Pointe Hospital	Warrensville Heights	Ohio
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	UPMC Cancer Center-Washington	Washington	Pennsylvania
United States	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	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	UPMC West Mifflin-Cancer Center Jefferson	West Mifflin	Pennsylvania
United States	Reading Hospital	West Reading	Pennsylvania
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Wexford Health and Wellness Pavilion	Wexford	Pennsylvania
United States	Presbyterian Intercommunity Hospital	Whittier	California
United States	Novant Health Cancer Institute - Wilkesboro	Wilkesboro	North Carolina
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Woodland Memorial Hospital	Woodland	California
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
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 (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percent change in mean volumetric apparent diffusion coefficient (ADC)	The study will assess the area under the receiver operating characteristic curve of the changes of ADC value.	Baseline to mid-treatment
Primary	Pathologic complete response (Step I)	The study with compare the pathologic complete response of Arm A and Arm B using a one-sided 0.10 level chi-squared test for proportions.	Up to 5 weeks
Primary	Disease-free survival (DFS) (Step 2)	DFS measured from the adjuvant treatment randomization will be the endpoint of the adjuvant portion of the study and to achieve the desired power it is expected that patients will be followed for an additional year post completion of accrual to the adjuvant portion. The DFS comparison will be between patients randomized to Arm C (nivolumab) versus Arm D (nivolumab plus ipilimumab) using a one-sided 0.10 level stratified log rank test.	From the adjuvant treatment randomization assessed for up to 7 years
Secondary	Incidence of adverse events	Graded according to Common Terminology Criteria for Adverse Events version 5.0. Toxicity will be evaluated among all treated patients regardless of eligibility and interim analyses of toxicity are performed twice yearly. The study will have sufficient precision to provide 95% confidence intervals on toxicity	Up to 7 years
Secondary	Overall survival	Analyses will be descriptive in nature and will not follow any formal interim monitoring.	From the time of first randomization up to 7 years
Secondary	DFS	The DFS comparison will be between patients randomized to Arm C (nivolumab) versus Arm D (nivolumab plus ipilimumab) using a one-sided 0.10 level stratified log rank test.	From the time of first randomization up to 7 years