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

Phase 2

Suspended

• Conditions: Clinical Stage II Esophageal Adenocarcinoma AJCC v8; Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Esophageal Adenocarcinoma; Clinical Stage IVA Esophageal Adenocarcinoma AJCC v8; Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage III Esophageal Adenocarcinoma AJCC v8; Gastroesophageal Junction Adenocarcinoma
• Interventions: Procedure: Biospecimen Collection; Drug: Carboplatin; Procedure: Computed Tomography; Biological: Ipilimumab; Biological: Nivolumab; Drug: Paclitaxel; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy

• Registration Number: NCT03604991
• Lead Sponsor: National Cancer Institute (NCI)

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2018-07-27
• Study First Submitted QC: 2018-07-27
• Study First Posted: 2018-07-30
• Study Start: 2019-05-03
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-21
• Last Update Posted: 2024-12-27
• Primary Completion: 2026-01-31
• Study Completion: 2026-01-31

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 278

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

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (carboplatin, paclitaxel, radiation therapy)	Positron Emission Tomography	Patients receive carboplatin IV and paclitaxel IV once weekly and undergo radiation therapy 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 CT or PET scan during screening and follow-up and undergo collection of blood samples throughout the trial.
Arm C (nivolumab)	Biospecimen Collection	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 B (carboplatin, paclitaxel, radiation therapy, nivolumab)	Positron Emission Tomography	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.
Arm A (carboplatin, paclitaxel, radiation therapy)	Computed Tomography	Patients receive carboplatin IV and paclitaxel IV once weekly and undergo radiation therapy 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 CT or PET scan during screening and follow-up and undergo collection of blood samples throughout the trial.
Arm B (carboplatin, paclitaxel, radiation therapy, nivolumab)	Radiation Therapy	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.
Arm D (nivolumab, ipilimumab)	Computed Tomography	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.
Arm A (carboplatin, paclitaxel, radiation therapy)	Biospecimen Collection	Patients receive carboplatin IV and paclitaxel IV once weekly and undergo radiation therapy 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 CT or PET scan during screening and follow-up and undergo collection of blood samples throughout the trial.
Arm A (carboplatin, paclitaxel, radiation therapy)	Radiation Therapy	Patients receive carboplatin IV and paclitaxel IV once weekly and undergo radiation therapy 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 CT or PET scan during screening and follow-up and undergo collection of blood samples throughout the trial.
Arm B (carboplatin, paclitaxel, radiation therapy, nivolumab)	Biospecimen Collection	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.
Arm B (carboplatin, paclitaxel, radiation therapy, nivolumab)	Computed Tomography	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.
Arm C (nivolumab)	Computed Tomography	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 (nivolumab, ipilimumab)	Biospecimen Collection	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.
Arm D (nivolumab, ipilimumab)	Nivolumab	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.
Arm A (carboplatin, paclitaxel, radiation therapy)	Carboplatin	Patients receive carboplatin IV and paclitaxel IV once weekly and undergo radiation therapy 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 CT or PET scan during screening and follow-up and undergo collection of blood samples throughout the trial.
Arm A (carboplatin, paclitaxel, radiation therapy)	Paclitaxel	Patients receive carboplatin IV and paclitaxel IV once weekly and undergo radiation therapy 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 CT or PET scan during screening and follow-up and undergo collection of blood samples throughout the trial.
Arm B (carboplatin, paclitaxel, radiation therapy, nivolumab)	Carboplatin	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.
Arm B (carboplatin, paclitaxel, radiation therapy, nivolumab)	Nivolumab	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.
Arm B (carboplatin, paclitaxel, radiation therapy, nivolumab)	Paclitaxel	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.
Arm C (nivolumab)	Nivolumab	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 (nivolumab, ipilimumab)	Ipilimumab	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.

Primary Outcome Measures

Name	Time	Method
Disease-free survival (DFS) (Step 2)	From the adjuvant treatment randomization assessed for up to 7 years	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.
Pathologic complete response (Step I)	Up to 5 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Incidence of adverse events	Up to 7 years	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
Overall survival	From the time of first randomization up to 7 years	Analyses will be descriptive in nature and will not follow any formal interim monitoring.
DFS	From the time of first randomization up to 7 years	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.

Trial Locations

Locations (490)

Anchorage Associates in Radiation Medicine; 🇺🇸 Anchorage, Alaska, 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 Oncology Centre; 🇺🇸 Anchorage, Alaska, United States

Katmai Oncology Group; 🇺🇸 Anchorage, Alaska, United States

Providence Alaska Medical Center; 🇺🇸 Anchorage, Alaska, United States

Cancer Center at Saint Joseph's; 🇺🇸 Phoenix, Arizona, United States

Mercy Hospital Fort Smith; 🇺🇸 Fort Smith, Arkansas, United States

CHI Saint Vincent Cancer Center Hot Springs; 🇺🇸 Hot Springs, Arkansas, United States

NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro; 🇺🇸 Jonesboro, Arkansas, United States

PCR Oncology; 🇺🇸 Arroyo Grande, California, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center; 🇺🇸 Burbank, California, United States

Community Cancer Institute; 🇺🇸 Clovis, California, United States

University Oncology Associates; 🇺🇸 Clovis, California, United States

Los Angeles General Medical Center; 🇺🇸 Los Angeles, California, United States

USC / Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Stanford Cancer Institute Palo Alto; 🇺🇸 Palo Alto, California, United States

VA Palo Alto Health Care System; 🇺🇸 Palo Alto, California, United States

Mercy Cancer Center - Sacramento; 🇺🇸 Sacramento, California, United States

University of California Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States

Saint Helena Hospital; 🇺🇸 Saint Helena, California, United States

Pacific Central Coast Health Center-San Luis Obispo; 🇺🇸 San Luis Obispo, California, United States

Mission Hope Medical Oncology - Santa Maria; 🇺🇸 Santa Maria, California, United States

Presbyterian Intercommunity Hospital; 🇺🇸 Whittier, California, United States

Woodland Memorial Hospital; 🇺🇸 Woodland, California, 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; 🇺🇸 Greenville, South Carolina, United States

Porter Adventist Hospital; 🇺🇸 Denver, Colorado, United States

Saint Anthony Hospital; 🇺🇸 Lakewood, Colorado, United States

Littleton Adventist Hospital; 🇺🇸 Littleton, Colorado, United States

Longmont United Hospital; 🇺🇸 Longmont, Colorado, United States

Parker Adventist Hospital; 🇺🇸 Parker, Colorado, United States

Saint Mary Corwin Medical Center; 🇺🇸 Pueblo, Colorado, United States

Beebe Medical Center; 🇺🇸 Lewes, Delaware, United States

Beebe South Coastal Health Campus; 🇺🇸 Millville, 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

Christiana Care Health System-Christiana Hospital; 🇺🇸 Newark, Delaware, United States

Beebe Health Campus; 🇺🇸 Rehoboth Beach, Delaware, United States

TidalHealth Nanticoke / Allen Cancer Center; 🇺🇸 Seaford, Delaware, United States

MedStar Georgetown University Hospital; 🇺🇸 Washington, District of Columbia, United States

AdventHealth Altamonte; 🇺🇸 Altamonte Springs, Florida, United States

Mount Sinai Comprehensive Cancer Center at Aventura; 🇺🇸 Aventura, Florida, United States

Holy Cross Hospital; 🇺🇸 Fort Lauderdale, Florida, United States

Regional Cancer Center-Lee Memorial Health System; 🇺🇸 Fort Myers, Florida, United States

University of Florida Health Science Center - Gainesville; 🇺🇸 Gainesville, Florida, United States

AdventHealth Kissimmee; 🇺🇸 Kissimmee, Florida, United States

Mount Sinai Medical Center; 🇺🇸 Miami Beach, Florida, United States

AdventHealth Orlando; 🇺🇸 Orlando, Florida, United States

AdventHealth East Orlando; 🇺🇸 Orlando, Florida, United States

Emory Proton Therapy Center; 🇺🇸 Atlanta, Georgia, United States

Emory University Hospital Midtown; 🇺🇸 Atlanta, Georgia, United States

Emory University Hospital/Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

Emory Saint Joseph's Hospital; 🇺🇸 Atlanta, Georgia, United States

Lewis Cancer and Research Pavilion at Saint Joseph's/Candler; 🇺🇸 Savannah, Georgia, 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

Hawaii Cancer Care Inc - Waterfront Plaza; 🇺🇸 Honolulu, Hawaii, United States

Island Urology; 🇺🇸 Honolulu, Hawaii, United States

Queen's Cancer Cenrer - POB I; 🇺🇸 Honolulu, Hawaii, United States

Queen's Medical Center; 🇺🇸 Honolulu, Hawaii, United States

Straub Clinic and Hospital; 🇺🇸 Honolulu, Hawaii, United States

University of Hawaii Cancer Center; 🇺🇸 Honolulu, Hawaii, United States

Hawaii Cancer Care Inc-Liliha; 🇺🇸 Honolulu, Hawaii, United States

Kuakini Medical Center; 🇺🇸 Honolulu, Hawaii, United States

Queen's Cancer Center - Kuakini; 🇺🇸 Honolulu, Hawaii, United States

The Cancer Center of Hawaii-Liliha; 🇺🇸 Honolulu, Hawaii, United States

Kapiolani Medical Center for Women and Children; 🇺🇸 Honolulu, Hawaii, United States

Wilcox Memorial Hospital and Kauai Medical Clinic; 🇺🇸 Lihue, Hawaii, United States

Saint Luke's Cancer Institute - Boise; 🇺🇸 Boise, Idaho, United States

Saint Luke's Cancer Institute - Fruitland; 🇺🇸 Fruitland, Idaho, United States

Saint Luke's Cancer Institute - Meridian; 🇺🇸 Meridian, Idaho, United States

Saint Luke's Cancer Institute - Nampa; 🇺🇸 Nampa, Idaho, United States

Saint Luke's Cancer Institute - Twin Falls; 🇺🇸 Twin Falls, Idaho, United States

Illinois CancerCare-Bloomington; 🇺🇸 Bloomington, Illinois, United States

Illinois CancerCare-Canton; 🇺🇸 Canton, Illinois, United States

Memorial Hospital of Carbondale; 🇺🇸 Carbondale, Illinois, United States

SIH Cancer Institute; 🇺🇸 Carterville, Illinois, United States

Illinois CancerCare-Carthage; 🇺🇸 Carthage, Illinois, United States

Centralia Oncology Clinic; 🇺🇸 Centralia, Illinois, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

University of Illinois; 🇺🇸 Chicago, Illinois, United States

Cancer Care Specialists of Illinois - Decatur; 🇺🇸 Decatur, Illinois, United States

Decatur Memorial Hospital; 🇺🇸 Decatur, Illinois, United States

Illinois CancerCare-Dixon; 🇺🇸 Dixon, Illinois, United States

Crossroads Cancer Center; 🇺🇸 Effingham, Illinois, United States

Illinois CancerCare-Eureka; 🇺🇸 Eureka, Illinois, United States

Illinois CancerCare-Galesburg; 🇺🇸 Galesburg, Illinois, United States

Western Illinois Cancer Treatment Center; 🇺🇸 Galesburg, Illinois, United States

Edward Hines Jr VA Hospital; 🇺🇸 Hines, Illinois, United States

Illinois CancerCare-Kewanee Clinic; 🇺🇸 Kewanee, Illinois, United States

Northwestern Medicine Lake Forest Hospital; 🇺🇸 Lake Forest, Illinois, United States

Illinois CancerCare-Macomb; 🇺🇸 Macomb, Illinois, United States

Loyola University Medical Center; 🇺🇸 Maywood, Illinois, United States

Good Samaritan Regional Health Center; 🇺🇸 Mount Vernon, Illinois, United States

Cancer Care Center of O'Fallon; 🇺🇸 O'Fallon, Illinois, United States

Illinois CancerCare-Ottawa Clinic; 🇺🇸 Ottawa, Illinois, 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

OSF Saint Francis Radiation Oncology at Peoria Cancer Center; 🇺🇸 Peoria, Illinois, United States

Methodist Medical Center of Illinois; 🇺🇸 Peoria, Illinois, United States

OSF Saint Francis Medical Center; 🇺🇸 Peoria, Illinois, United States

Illinois CancerCare-Peru; 🇺🇸 Peru, Illinois, United States

Valley Radiation Oncology; 🇺🇸 Peru, Illinois, United States

Illinois CancerCare-Princeton; 🇺🇸 Princeton, Illinois, United States

Southern Illinois University School of Medicine; 🇺🇸 Springfield, Illinois, United States

Springfield Clinic; 🇺🇸 Springfield, Illinois, United States

Springfield Memorial Hospital; 🇺🇸 Springfield, Illinois, United States

Illinois CancerCare - Washington; 🇺🇸 Washington, Illinois, United States

IU Health North Hospital; 🇺🇸 Carmel, Indiana, United States

Indiana University/Melvin and Bren Simon Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

Reid Health; 🇺🇸 Richmond, Indiana, United States

Mercy Cancer Center-West Lakes; 🇺🇸 Clive, Iowa, United States

Mission Cancer and Blood - West Des Moines; 🇺🇸 Clive, Iowa, United States

Greater Regional Medical Center; 🇺🇸 Creston, Iowa, United States

Mercy Medical Center - Des Moines; 🇺🇸 Des Moines, Iowa, United States

Mission Cancer and Blood - Laurel; 🇺🇸 Des Moines, Iowa, United States

Mercy Medical Center-West Lakes; 🇺🇸 West Des Moines, Iowa, United States

Central Care Cancer Center - Garden City; 🇺🇸 Garden City, Kansas, United States

Central Care Cancer Center - Great Bend; 🇺🇸 Great Bend, Kansas, United States

Saint Joseph Hospital; 🇺🇸 Lexington, Kentucky, United States

Saint Joseph Radiation Oncology Resource Center; 🇺🇸 Lexington, Kentucky, United States

Saint Joseph Hospital East; 🇺🇸 Lexington, Kentucky, United States

Jewish Hospital; 🇺🇸 Louisville, Kentucky, United States

UofL Health Medical Center Northeast; 🇺🇸 Louisville, Kentucky, United States

Ochsner Medical Center Kenner; 🇺🇸 Kenner, Louisiana, United States

Ochsner Medical Center Jefferson; 🇺🇸 New Orleans, Louisiana, United States

Eastern Maine Medical Center; 🇺🇸 Bangor, Maine, United States

MaineHealth Coastal Cancer Treatment Center; 🇺🇸 Bath, Maine, United States

MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford; 🇺🇸 Biddeford, Maine, United States

Lafayette Family Cancer Center-EMMC; 🇺🇸 Brewer, Maine, United States

Maine Medical Center-Bramhall Campus; 🇺🇸 Portland, Maine, 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

Maine Medical Center- Scarborough Campus; 🇺🇸 Scarborough, Maine, United States

Maine Medical Partners - South Portland; 🇺🇸 South Portland, Maine, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Boston Medical Center; 🇺🇸 Boston, Massachusetts, United States

Lowell General Hospital; 🇺🇸 Lowell, Massachusetts, United States

Trinity Health Saint Joseph Mercy Hospital Ann Arbor; 🇺🇸 Ann Arbor, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Brighton; 🇺🇸 Brighton, Michigan, United States

Trinity Health Medical Center - Brighton; 🇺🇸 Brighton, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Canton; 🇺🇸 Canton, Michigan, United States

Trinity Health Medical Center - Canton; 🇺🇸 Canton, Michigan, United States

Caro Cancer Center; 🇺🇸 Caro, Michigan, United States

Chelsea Hospital; 🇺🇸 Chelsea, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital; 🇺🇸 Chelsea, Michigan, United States

Henry Ford Health Saint John Hospital; 🇺🇸 Detroit, Michigan, United States

Genesys Hurley Cancer Institute; 🇺🇸 Flint, Michigan, United States

Hurley Medical Center; 🇺🇸 Flint, Michigan, United States

Henry Ford Saint John Hospital - Van Elslander; 🇺🇸 Grosse Pointe Woods, Michigan, United States

University of Michigan Health - Sparrow Lansing; 🇺🇸 Lansing, Michigan, United States

Trinity Health Saint Mary Mercy Livonia Hospital; 🇺🇸 Livonia, Michigan, United States

Henry Ford Saint John Hospital - Macomb Medical; 🇺🇸 Macomb, Michigan, United States

Saint Mary's Oncology/Hematology Associates of Marlette; 🇺🇸 Marlette, Michigan, United States

Henry Ford Health Providence Novi Hospital; 🇺🇸 Novi, Michigan, United States

Michigan Healthcare Professionals Pontiac; 🇺🇸 Pontiac, Michigan, United States

Trinity Health Saint Joseph Mercy Oakland Hospital; 🇺🇸 Pontiac, Michigan, United States

MyMichigan Medical Center Saginaw; 🇺🇸 Saginaw, Michigan, United States

Oncology Hematology Associates of Saginaw Valley PC; 🇺🇸 Saginaw, Michigan, United States

Henry Ford Health Providence Southfield Hospital; 🇺🇸 Southfield, Michigan, United States

MyMichigan Medical Center Tawas; 🇺🇸 Tawas City, Michigan, United States

Henry Ford Health Warren Hospital; 🇺🇸 Warren, Michigan, United States

Saint Mary's Oncology/Hematology Associates of West Branch; 🇺🇸 West Branch, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus; 🇺🇸 Ypsilanti, Michigan, United States

Sanford Joe Lueken Cancer Center; 🇺🇸 Bemidji, Minnesota, United States

Essentia Health Saint Joseph's Medical Center; 🇺🇸 Brainerd, Minnesota, United States

Fairview Ridges Hospital; 🇺🇸 Burnsville, Minnesota, United States

Minnesota Oncology - Burnsville; 🇺🇸 Burnsville, Minnesota, United States

Mercy Hospital; 🇺🇸 Coon Rapids, Minnesota, United States

Essentia Health - Deer River Clinic; 🇺🇸 Deer River, Minnesota, United States

Essentia Health Saint Mary's - Detroit Lakes Clinic; 🇺🇸 Detroit Lakes, Minnesota, 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

Fairview Southdale Hospital; 🇺🇸 Edina, Minnesota, United States

Lake Region Healthcare Corporation-Cancer Care; 🇺🇸 Fergus Falls, Minnesota, United States

Essentia Health - Fosston; 🇺🇸 Fosston, Minnesota, United States

Unity Hospital; 🇺🇸 Fridley, Minnesota, United States

Essentia Health Hibbing Clinic; 🇺🇸 Hibbing, Minnesota, 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

Abbott-Northwestern Hospital; 🇺🇸 Minneapolis, Minnesota, United States

Hennepin County Medical Center; 🇺🇸 Minneapolis, Minnesota, United States

Health Partners Inc; 🇺🇸 Minneapolis, Minnesota, United States

Monticello Cancer Center; 🇺🇸 Monticello, Minnesota, United States

Essentia Health - Park Rapids; 🇺🇸 Park Rapids, Minnesota, United States

North Memorial Medical Health Center; 🇺🇸 Robbinsdale, Minnesota, United States

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, 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

Essentia Health Sandstone; 🇺🇸 Sandstone, Minnesota, United States

Saint Francis Regional Medical Center; 🇺🇸 Shakopee, Minnesota, United States

Lakeview Hospital; 🇺🇸 Stillwater, Minnesota, United States

Essentia Health Virginia Clinic; 🇺🇸 Virginia, Minnesota, United States

Ridgeview Medical Center; 🇺🇸 Waconia, Minnesota, United States

Rice Memorial Hospital; 🇺🇸 Willmar, Minnesota, United States

Minnesota Oncology Hematology PA-Woodbury; 🇺🇸 Woodbury, Minnesota, United States

Baptist Memorial Hospital and Cancer Center-Golden Triangle; 🇺🇸 Columbus, Mississippi, United States

Baptist Cancer Center-Grenada; 🇺🇸 Grenada, Mississippi, United States

Baptist Memorial Hospital and Cancer Center-Union County; 🇺🇸 New Albany, Mississippi, United States

Baptist Memorial Hospital and Cancer Center-Oxford; 🇺🇸 Oxford, Mississippi, United States

Baptist Memorial Hospital and Cancer Center-Desoto; 🇺🇸 Southhaven, Mississippi, United States

Saint Louis Cancer and Breast Institute-Ballwin; 🇺🇸 Ballwin, Missouri, United States

Central Care Cancer Center - Bolivar; 🇺🇸 Bolivar, Missouri, United States

Saint Francis Medical Center; 🇺🇸 Cape Girardeau, Missouri, United States

Southeast Cancer Center; 🇺🇸 Cape Girardeau, Missouri, United States

Siteman Cancer Center at West County Hospital; 🇺🇸 Creve Coeur, Missouri, United States

Parkland Health Center - Farmington; 🇺🇸 Farmington, Missouri, United States

MU Health Care Goldschmidt Cancer Center; 🇺🇸 Jefferson City, Missouri, United States

Freeman Health System; 🇺🇸 Joplin, Missouri, United States

Mercy Hospital Joplin; 🇺🇸 Joplin, Missouri, United States

Delbert Day Cancer Institute at PCRMC; 🇺🇸 Rolla, Missouri, United States

Mercy Clinic-Rolla-Cancer and Hematology; 🇺🇸 Rolla, Missouri, United States

Heartland Regional Medical Center; 🇺🇸 Saint Joseph, Missouri, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Mercy Hospital South; 🇺🇸 Saint Louis, Missouri, United States

Siteman Cancer Center-South County; 🇺🇸 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

Mercy Hospital Saint Louis; 🇺🇸 Saint Louis, Missouri, United States

Siteman Cancer Center at Saint Peters Hospital; 🇺🇸 Saint Peters, Missouri, United States

Sainte Genevieve County Memorial Hospital; 🇺🇸 Sainte Genevieve, Missouri, United States

Mercy Hospital Springfield; 🇺🇸 Springfield, Missouri, United States

CoxHealth South Hospital; 🇺🇸 Springfield, Missouri, United States

Missouri Baptist Sullivan Hospital; 🇺🇸 Sullivan, Missouri, United States

BJC Outpatient Center at Sunset Hills; 🇺🇸 Sunset Hills, Missouri, United States

Saint Patrick Hospital - Community Hospital; 🇺🇸 Missoula, Montana, United States

Nebraska Medicine-Bellevue; 🇺🇸 Bellevue, Nebraska, United States

Nebraska Cancer Specialists/Oncology Hematology West PC; 🇺🇸 Grand Island, Nebraska, United States

CHI Health Good Samaritan; 🇺🇸 Kearney, Nebraska, United States

Nebraska Medicine-Village Pointe; 🇺🇸 Omaha, Nebraska, United States

Alegent Health Immanuel Medical Center; 🇺🇸 Omaha, Nebraska, United States

Alegent Health Bergan Mercy Medical Center; 🇺🇸 Omaha, Nebraska, United States

Alegent Health Lakeside Hospital; 🇺🇸 Omaha, Nebraska, United States

Creighton University Medical Center; 🇺🇸 Omaha, Nebraska, United States

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States

Comprehensive Cancer Centers of Nevada - Henderson; 🇺🇸 Henderson, Nevada, United States

OptumCare Cancer Care at Seven Hills; 🇺🇸 Henderson, Nevada, United States

OptumCare Cancer Care at Charleston; 🇺🇸 Las Vegas, Nevada, United States

Radiation Oncology Centers of Nevada Central; 🇺🇸 Las Vegas, Nevada, United States

GenesisCare USA - Las Vegas; 🇺🇸 Las Vegas, Nevada, United States

Radiation Oncology Centers of Nevada Southeast; 🇺🇸 Las Vegas, Nevada, United States

Comprehensive Cancer Centers of Nevada - Northwest; 🇺🇸 Las Vegas, Nevada, United States

OptumCare Cancer Care at MountainView; 🇺🇸 Las Vegas, Nevada, United States

Alliance for Childhood Diseases/Cure 4 the Kids Foundation; 🇺🇸 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

Comprehensive Cancer Centers of Nevada; 🇺🇸 Las Vegas, Nevada, United States

OptumCare Cancer Care at Fort Apache; 🇺🇸 Las Vegas, Nevada, United States

Comprehensive Cancer Centers of Nevada - Central Valley; 🇺🇸 Las Vegas, Nevada, United States

Renown Regional Medical Center; 🇺🇸 Reno, Nevada, United States

Saint Mary's Regional Medical Center; 🇺🇸 Reno, Nevada, United States

Radiation Oncology Associates; 🇺🇸 Reno, Nevada, United States

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center; 🇺🇸 Lebanon, New Hampshire, United States

Ocean University Medical Center; 🇺🇸 Brick, New Jersey, United States

Monmouth Medical Center; 🇺🇸 Long Branch, New Jersey, United States

Southern Ocean County Medical Center; 🇺🇸 Manahawkin, New Jersey, United States

Jersey Shore Medical Center; 🇺🇸 Neptune, New Jersey, United States

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States

Riverview Medical Center/Booker Cancer Center; 🇺🇸 Red Bank, New Jersey, United States

Community Medical Center; 🇺🇸 Toms River, New Jersey, United States

Lovelace Medical Center-Saint Joseph Square; 🇺🇸 Albuquerque, New Mexico, United States

University of New Mexico Cancer Center; 🇺🇸 Albuquerque, New Mexico, United States

New Mexico Oncology Hematology Consultants; 🇺🇸 Albuquerque, New Mexico, United States

Presbyterian Kaseman Hospital; 🇺🇸 Albuquerque, New Mexico, United States

Presbyterian Rust Medical Center/Jorgensen Cancer Center; 🇺🇸 Rio Rancho, New Mexico, United States

Montefiore Medical Center-Einstein Campus; 🇺🇸 Bronx, New York, United States

Montefiore Medical Center-Weiler Hospital; 🇺🇸 Bronx, New York, United States

Montefiore Medical Center - Moses Campus; 🇺🇸 Bronx, New York, United States

Sands Cancer Center; 🇺🇸 Canandaigua, New York, United States

Noyes Memorial Hospital/Myers Cancer Center; 🇺🇸 Dansville, New York, United States

Glens Falls Hospital; 🇺🇸 Glens Falls, New York, United States

Northwell Health/Center for Advanced Medicine; 🇺🇸 Lake Success, New York, United States

Garnet Health Medical Center; 🇺🇸 Middletown, New York, 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

University of Rochester; 🇺🇸 Rochester, New York, United States

State University of New York Upstate Medical University; 🇺🇸 Syracuse, New York, United States

Novant Health Presbyterian Medical Center; 🇺🇸 Charlotte, North Carolina, United States

Novant Health Cancer Institute - Huntersville; 🇺🇸 Huntersville, North Carolina, United States

Novant Health Presbyterian Medical Center Huntersville; 🇺🇸 Huntersville, North Carolina, United States

Novant Health Cancer Institute - Kernersville; 🇺🇸 Kernersville, North Carolina, United States

Matthews Radiation Oncology Center; 🇺🇸 Matthews, North Carolina, United States

Novant Health Cancer Institute - Matthews; 🇺🇸 Matthews, North Carolina, United States

Novant Health Cancer Institute - Mooresville; 🇺🇸 Mooresville, North Carolina, United States

Novant Health Cancer Institute - Mount Airy; 🇺🇸 Mount Airy, North Carolina, United States

Novant Health Cancer Institute - Wilkesboro; 🇺🇸 North Wilkesboro, North Carolina, United States

Rowan Regional Medical Center; 🇺🇸 Salisbury, North Carolina, United States

Novant Health Cancer Institute - Statesville; 🇺🇸 Statesville, North Carolina, United States

Novant Health Cancer Institute - Thomasville; 🇺🇸 Thomasville, North Carolina, United States

Novant Health Forsyth Medical Center; 🇺🇸 Winston-Salem, North Carolina, United States

Sanford Bismarck Medical Center; 🇺🇸 Bismarck, North Dakota, 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

Essentia Health - Jamestown Clinic; 🇺🇸 Jamestown, North Dakota, United States

Indu and Raj Soin Medical Center; 🇺🇸 Beavercreek, Ohio, United States

Saint Elizabeth Boardman Hospital; 🇺🇸 Boardman, Ohio, United States

Dayton Physicians LLC-Miami Valley South; 🇺🇸 Centerville, Ohio, United States

Miami Valley Hospital South; 🇺🇸 Centerville, Ohio, United States

University of Cincinnati Cancer Center-UC Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Good Samaritan Hospital - Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Oncology Hematology Care Inc-Kenwood; 🇺🇸 Cincinnati, Ohio, United States

Bethesda North Hospital; 🇺🇸 Cincinnati, Ohio, United States

MetroHealth Medical Center; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Cancer Center/Fairview Hospital; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

Miami Valley Hospital; 🇺🇸 Dayton, Ohio, United States

Dayton Physician LLC - Englewood; 🇺🇸 Dayton, Ohio, United States

Miami Valley Hospital North; 🇺🇸 Dayton, Ohio, United States

Armes Family Cancer Center; 🇺🇸 Findlay, Ohio, United States

Blanchard Valley Hospital; 🇺🇸 Findlay, Ohio, United States

Orion Cancer Care; 🇺🇸 Findlay, Ohio, United States

Atrium Medical Center-Middletown Regional Hospital; 🇺🇸 Franklin, Ohio, United States

Dayton Physicians LLC-Atrium; 🇺🇸 Franklin, Ohio, United States

Dayton Physicians LLC-Wayne; 🇺🇸 Greenville, Ohio, United States

Wayne Hospital; 🇺🇸 Greenville, Ohio, United States

Cleveland Clinic Cancer Center Independence; 🇺🇸 Independence, Ohio, United States

Greater Dayton Cancer Center; 🇺🇸 Kettering, Ohio, United States

Kettering Medical Center; 🇺🇸 Kettering, Ohio, United States

Cleveland Clinic Cancer Center Mansfield; 🇺🇸 Mansfield, Ohio, United States

Hillcrest Hospital Cancer Center; 🇺🇸 Mayfield Heights, Ohio, United States

North Coast Cancer Care; 🇺🇸 Sandusky, Ohio, United States

Springfield Regional Cancer Center; 🇺🇸 Springfield, Ohio, United States

Springfield Regional Medical Center; 🇺🇸 Springfield, Ohio, United States

Cleveland Clinic Cancer Center Strongsville; 🇺🇸 Strongsville, Ohio, United States

ProMedica Flower Hospital; 🇺🇸 Sylvania, Ohio, United States

ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital; 🇺🇸 Toledo, Ohio, United States

Dayton Physicians LLC - Troy; 🇺🇸 Troy, Ohio, United States

Upper Valley Medical Center; 🇺🇸 Troy, Ohio, United States

South Pointe Hospital; 🇺🇸 Warrensville Heights, Ohio, United States

Saint Joseph Warren Hospital; 🇺🇸 Warren, Ohio, United States

University of Cincinnati Cancer Center-West Chester; 🇺🇸 West Chester, Ohio, United States

Cleveland Clinic Wooster Family Health and Surgery Center; 🇺🇸 Wooster, Ohio, United States

Saint Elizabeth Youngstown Hospital; 🇺🇸 Youngstown, Ohio, United States

Mercy Hospital Oklahoma City; 🇺🇸 Oklahoma City, Oklahoma, United States

Saint Charles Health System; 🇺🇸 Bend, Oregon, United States

Clackamas Radiation Oncology Center; 🇺🇸 Clackamas, Oregon, United States

Providence Cancer Institute Clackamas Clinic; 🇺🇸 Clackamas, Oregon, United States

Bay Area Hospital; 🇺🇸 Coos Bay, Oregon, United States

Providence Newberg Medical Center; 🇺🇸 Newberg, Oregon, United States

Providence Portland Medical Center; 🇺🇸 Portland, Oregon, United States

Providence Saint Vincent Medical Center; 🇺🇸 Portland, Oregon, United States

Lehigh Valley Hospital-Cedar Crest; 🇺🇸 Allentown, Pennsylvania, United States

Saint Luke's Cancer Center - Allentown; 🇺🇸 Allentown, Pennsylvania, United States

UPMC Altoona; 🇺🇸 Altoona, Pennsylvania, United States

UPMC-Heritage Valley Health System Beaver; 🇺🇸 Beaver, Pennsylvania, United States

Saint Luke's University Hospital-Bethlehem Campus; 🇺🇸 Bethlehem, Pennsylvania, United States

Lehigh Valley Hospital - Muhlenberg; 🇺🇸 Bethlehem, Pennsylvania, United States

UPMC Hillman Cancer Center at Butler Health System; 🇺🇸 Butler, Pennsylvania, United States

UPMC Camp Hill; 🇺🇸 Camp Hill, Pennsylvania, United States

Carlisle Regional Cancer Center; 🇺🇸 Carlisle, Pennsylvania, United States

Christiana Care Health System-Concord Health Center; 🇺🇸 Chadds Ford, Pennsylvania, United States

Geisinger Medical Center; 🇺🇸 Danville, Pennsylvania, United States

Pocono Medical Center; 🇺🇸 East Stroudsburg, Pennsylvania, United States

Saint Luke's Hospital-Anderson Campus; 🇺🇸 Easton, Pennsylvania, United States

UPMC Hillman Cancer Center Erie; 🇺🇸 Erie, Pennsylvania, United States

UPMC Cancer Center at UPMC Horizon; 🇺🇸 Farrell, Pennsylvania, United States

UPMC Cancer Centers - Arnold Palmer Pavilion; 🇺🇸 Greensburg, Pennsylvania, United States

UPMC Pinnacle Cancer Center/Community Osteopathic Campus; 🇺🇸 Harrisburg, Pennsylvania, United States

Penn State Milton S Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

IRMC Cancer Center; 🇺🇸 Indiana, Pennsylvania, United States

Jefferson Hospital; 🇺🇸 Jefferson Hills, Pennsylvania, United States

UPMC-Johnstown/John P. Murtha Regional Cancer Center; 🇺🇸 Johnstown, Pennsylvania, United States

Geisinger Medical Oncology-Lewisburg; 🇺🇸 Lewisburg, Pennsylvania, United States

UPMC Cancer Center at UPMC McKeesport; 🇺🇸 McKeesport, Pennsylvania, 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

UPMC Hillman Cancer Center in Coraopolis; 🇺🇸 Moon, Pennsylvania, United States

UPMC Hillman Cancer Center - Part of Frick Hospital; 🇺🇸 Mount Pleasant, Pennsylvania, United States

Arnold Palmer Cancer Center Medical Oncology Norwin; 🇺🇸 N. Huntingdon, Pennsylvania, United States

Allegheny Valley Hospital; 🇺🇸 Natrona Heights, Pennsylvania, United States

UPMC Hillman Cancer Center - New Castle; 🇺🇸 New Castle, Pennsylvania, United States

University of Pennsylvania/Abramson Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Allegheny General Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC-Magee Womens Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC-Saint Margaret; 🇺🇸 Pittsburgh, Pennsylvania, United States

West Penn Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Pittsburgh Cancer Institute (UPCI); 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC-Shadyside Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC-Passavant Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC-Saint Clair Hospital Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Pottstown Hospital; 🇺🇸 Pottstown, Pennsylvania, United States

UPMC Cancer Center at UPMC Northwest; 🇺🇸 Seneca, Pennsylvania, United States

UPMC Cancer Center-Uniontown; 🇺🇸 Uniontown, Pennsylvania, United States

UPMC Uniontown Hospital Radiation Oncology; 🇺🇸 Uniontown, Pennsylvania, United States

UPMC Cancer Center-Washington; 🇺🇸 Washington, Pennsylvania, United States

UPMC Washington Hospital Radiation Oncology; 🇺🇸 Washington, Pennsylvania, United States

UPMC West Mifflin-Cancer Center Jefferson; 🇺🇸 West Mifflin, Pennsylvania, United States

Reading Hospital; 🇺🇸 West Reading, Pennsylvania, United States

Wexford Health and Wellness Pavilion; 🇺🇸 Wexford, Pennsylvania, United States

UPMC Memorial; 🇺🇸 York, Pennsylvania, United States

Rhode Island Hospital at East Greenwich; 🇺🇸 East Greenwich, Rhode Island, United States

Newport Hospital; 🇺🇸 Newport, Rhode Island, United States

Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Saint Francis Hospital; 🇺🇸 Greenville, South Carolina, United States

Sanford Cancer Center Oncology Clinic; 🇺🇸 Sioux Falls, South Dakota, United States

Avera Cancer Institute; 🇺🇸 Sioux Falls, South Dakota, United States

Sanford USD Medical Center - Sioux Falls; 🇺🇸 Sioux Falls, South Dakota, United States

Baptist Memorial Hospital and Cancer Center-Collierville; 🇺🇸 Collierville, Tennessee, United States

Baptist Memorial Hospital and Cancer Center-Memphis; 🇺🇸 Memphis, Tennessee, United States

Vanderbilt University/Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

Saint Joseph Regional Cancer Center; 🇺🇸 Bryan, Texas, United States

Parkland Memorial Hospital; 🇺🇸 Dallas, Texas, United States

UT Southwestern/Simmons Cancer Center-Dallas; 🇺🇸 Dallas, Texas, United States

UT Southwestern/Simmons Cancer Center-Fort Worth; 🇺🇸 Fort Worth, Texas, United States

UT Southwestern Clinical Center at Richardson/Plano; 🇺🇸 Richardson, Texas, United States

University of Utah Sugarhouse Health Center; 🇺🇸 Salt Lake City, Utah, United States

Huntsman Cancer Institute/University of Utah; 🇺🇸 Salt Lake City, Utah, United States

Central Vermont Medical Center/National Life Cancer Treatment; 🇺🇸 Berlin, Vermont, United States

University of Vermont Medical Center; 🇺🇸 Burlington, Vermont, United States

University of Vermont and State Agricultural College; 🇺🇸 Burlington, Vermont, United States

Dartmouth Cancer Center - North; 🇺🇸 Saint Johnsbury, Vermont, United States

University of Virginia Cancer Center; 🇺🇸 Charlottesville, Virginia, United States

Virginia Cancer Institute; 🇺🇸 Richmond, Virginia, United States

Virginia Commonwealth University/Massey Cancer Center; 🇺🇸 Richmond, Virginia, United States

VCU Community Memorial Health Center; 🇺🇸 South Hill, Virginia, United States

Providence Regional Cancer System-Aberdeen; 🇺🇸 Aberdeen, Washington, United States

Overlake Medical Center; 🇺🇸 Bellevue, Washington, United States

PeaceHealth Saint Joseph Medical Center; 🇺🇸 Bellingham, Washington, United States

Harrison HealthPartners Hematology and Oncology-Bremerton; 🇺🇸 Bremerton, Washington, United States

Highline Medical Center-Main Campus; 🇺🇸 Burien, Washington, United States

Providence Regional Cancer System-Centralia; 🇺🇸 Centralia, Washington, United States

Swedish Cancer Institute-Edmonds; 🇺🇸 Edmonds, Washington, United States

Providence Regional Cancer Partnership; 🇺🇸 Everett, Washington, United States

Swedish Cancer Institute-Issaquah; 🇺🇸 Issaquah, Washington, United States

Providence Regional Cancer System-Lacey; 🇺🇸 Lacey, Washington, United States

PeaceHealth Saint John Medical Center; 🇺🇸 Longview, Washington, United States

Valley Medical Center; 🇺🇸 Renton, Washington, 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

Saint Michael Cancer Center; 🇺🇸 Silverdale, Washington, United States

Northwest Medical Specialties PLLC; 🇺🇸 Tacoma, Washington, United States

PeaceHealth Southwest Medical Center; 🇺🇸 Vancouver, Washington, United States

Providence Saint Mary Regional Cancer Center; 🇺🇸 Walla Walla, Washington, United States

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital; 🇺🇸 Yakima, Washington, United States

United Hospital Center; 🇺🇸 Bridgeport, West Virginia, United States

West Virginia University Charleston Division; 🇺🇸 Charleston, West Virginia, United States

West Virginia University Healthcare; 🇺🇸 Morgantown, West Virginia, United States

Camden Clark Medical Center; 🇺🇸 Parkersburg, West Virginia, United States

ThedaCare Regional Cancer Center; 🇺🇸 Appleton, Wisconsin, United States

Duluth Clinic Ashland; 🇺🇸 Ashland, Wisconsin, United States

Northwest Wisconsin Cancer Center; 🇺🇸 Ashland, Wisconsin, United States

Aurora Cancer Care-Southern Lakes VLCC; 🇺🇸 Burlington, Wisconsin, United States

HSHS Sacred Heart Hospital; 🇺🇸 Eau Claire, Wisconsin, United States

Marshfield Medical Center-EC Cancer Center; 🇺🇸 Eau Claire, Wisconsin, United States

Aurora Health Center-Fond du Lac; 🇺🇸 Fond Du Lac, Wisconsin, United States

Aurora Health Care Germantown Health Center; 🇺🇸 Germantown, Wisconsin, United States

Aurora Cancer Care-Grafton; 🇺🇸 Grafton, Wisconsin, United States

Bellin Memorial Hospital; 🇺🇸 Green Bay, Wisconsin, United States

Saint Vincent Hospital Cancer Center Green Bay; 🇺🇸 Green Bay, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Saint Mary's; 🇺🇸 Green Bay, Wisconsin, United States

Aurora BayCare Medical Center; 🇺🇸 Green Bay, Wisconsin, United States

Essentia Health-Hayward Clinic; 🇺🇸 Hayward, Wisconsin, United States

University of Wisconsin Carbone Cancer Center - Johnson Creek; 🇺🇸 Johnson Creek, Wisconsin, United States

Aurora Cancer Care-Kenosha South; 🇺🇸 Kenosha, Wisconsin, United States

University of Wisconsin Carbone Cancer Center - University Hospital; 🇺🇸 Madison, Wisconsin, United States

Aurora Bay Area Medical Group-Marinette; 🇺🇸 Marinette, Wisconsin, United States

Marshfield Medical Center-Marshfield; 🇺🇸 Marshfield, Wisconsin, 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

Marshfield Medical Center - Minocqua; 🇺🇸 Minocqua, Wisconsin, United States

Cancer Center of Western Wisconsin; 🇺🇸 New Richmond, Wisconsin, United States

Vince Lombardi Cancer Clinic - Oshkosh; 🇺🇸 Oshkosh, Wisconsin, United States

Aurora Cancer Care-Racine; 🇺🇸 Racine, Wisconsin, United States

Marshfield Medical Center-Rice Lake; 🇺🇸 Rice Lake, Wisconsin, United States

Vince Lombardi Cancer Clinic-Sheboygan; 🇺🇸 Sheboygan, Wisconsin, United States

Essentia Health-Spooner Clinic; 🇺🇸 Spooner, Wisconsin, United States

Marshfield Medical Center-River Region at Stevens Point; 🇺🇸 Stevens Point, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Sturgeon Bay; 🇺🇸 Sturgeon Bay, Wisconsin, United States

Aurora Medical Center in Summit; 🇺🇸 Summit, Wisconsin, United States

Essentia Health Saint Mary's Hospital - Superior; 🇺🇸 Superior, Wisconsin, United States

Vince Lombardi Cancer Clinic-Two Rivers; 🇺🇸 Two Rivers, Wisconsin, United States

Aurora Cancer Care-Milwaukee West; 🇺🇸 Wauwatosa, Wisconsin, United States

Aurora West Allis Medical Center; 🇺🇸 West Allis, Wisconsin, United States

Marshfield Medical Center - Weston; 🇺🇸 Weston, Wisconsin, United States