Trial Search Results

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

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.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Drug: Carboplatin
  • Biological: Ipilimumab
  • Biological: Nivolumab
  • Drug: Paclitaxel
  • Radiation: Radiation Therapy

Phase:

Phase 2/Phase 3

Eligibility


Inclusion Criteria:

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

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

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

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

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

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

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

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

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

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

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

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

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

   - STEP 1: 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, should 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 should 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 should be evaluated for the presence of target organ
   involvement and potential need for systemic treatment but should otherwise be eligible

   - STEP 1: 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: 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

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

      - Date of last evidence of disease

   - STEP 1: 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: 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: For patients with evidence of CHF, myocardial infarction (MI), cardiomyopathy,
   or myositis, cardiac evaluation including lab tests and cardiology consultations
   including EKG, creatine phosphokinase (CPK), troponin, and echocardiogram

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

   - STEP 1: 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: Women must not be pregnant or breast-feeding due to potential harm to the
   fetus from carboplatin, paclitaxel, or nivolumab. All females of childbearing
   potential must have a blood test or urine study done within 2 weeks prior to
   registration 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 female of childbearing potential is any woman, regardless of sexual
   orientation or whether they have undergone tubal ligation, who meets the following
   criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) 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: Women of childbearing potential (WOCBP) and sexually active males must either
   abstain from sexual intercourse for the duration of their participation in the study
   or agree to use both double barrier contraception and birth control pills or implants
   for at least one month (female patients) or one week (male patients) prior to the
   start of the study drug and continuing for 5 months after the last dose of study drug
   (for female patients) and for 7 months after the last dose of study drug (for male
   patients who are sexually active with WOCBP). Investigators shall counsel WOCBP and
   male subjects who are sexually active with WOCBP on the importance of pregnancy
   prevention and the implications of an unexpected pregnancy

   - STEP 1: If patient says 'Yes' to "I choose to take part in the imaging study and will
   have the diffusion weighted magnetic resonance imaging (MRI) scans": patients must be
   able to tolerate MRI scans:

      - No history of untreatable claustrophobia

      - No magnetic resonance (MR) incompatible implants/devices or metallic foreign
      bodies

      - Weight compatible with limits imposed by the MRI scanner table

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

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

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

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

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

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

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

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

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

   - STEP 2: 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: Women must not be pregnant or breast-feeding due to potential harm to the
   fetus from nivolumab or ipilimumab. All females 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 registration 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: Women of childbearing potential (WOCBP) and sexually active males must either
   abstain from sexual intercourse for the duration of their participation in the study
   or agree to use both double barrier contraception and birth control pills or implants
   for at least one month (female patients) or one week (male patients) prior to the
   start of the study drug and continuing for 5 months after the last dose of study drug
   (for female patients) and for 7 months after the last dose of study drug (for male
   patients who are sexually active with WOCBP). Investigators shall counsel WOCBP and
   male subjects who are sexually active with WOCBP on the importance of pregnancy
   prevention and the implications of an unexpected pregnancy

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Daniel Holguin
650-736-3379
Recruiting