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

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