This is a randomized phase II study examining nivolumab alone versus radiation therapy with
nivolumab in subjects who did not have disease progression to initial therapy with the
combination of FOLFOX and Nivolumab. Subjects with advanced unresectable or metastatic
gastroesophageal adenocarcinoma are eligible. All subjects will receive FOLFOX + nivolumab
therapy. Subjects who demonstrate at least stable disease, as per RECIST 1.1, on their first
imaging assessment at two months will receive one additional month of FOLFOX + nivolumab (3
months total), and then will be randomly assigned at a 1:1 ratio to receive either nivolumab
alone or nivolumab plus radiation therapy. Radiation therapy fields and technique will be
approved by central review. Radiation will be planned at 4Gy x 5 doses (20 Gy total), given
concurrently with nivolumab. After 4 months of therapy, patients who remain on study will
receive nivolumab 480 mg every 4 weeks. Subjects will be on study (intervention + follow-up)
for approximately 24 months. The projected end date of the study, including data analysis, is
- Subjects with a diagnosis of advanced unresectable or metastatic gastroesophageal
adenocarcinoma (eg. gastric, gastroesophageal junction, and esophageal adenocarcinoma)
- Be willing and able to provide written informed consent/assent for the trial
- Age > 18 years
- ECOG performance status ≤ 1
- Absolute neutrophil count ≥ 1,500/mL
- Platelets ≥ 100,000/mL
- Total bilirubin ≤ 1.5x upper limits of normal, unless the patient has known Gilbert's
- AST/ALT ≤ 2.5 upper limits of normal, or < 5x ULN for subjects with liver metastases
- Creatinine ≤ 1.5 mg/dl. If Creatinine > 1.5 mg/dl, creatinine clearance > 60 ml/min
- Be willing to provide tissue from a newly obtained core or excisional biopsy of a
tumor lesion. Newly-obtained is defined as a specimen obtained up to 28 days prior to
initiation of treatment on Day 1.
- For all males and females of childbearing potential, they should be agreeable to use
an adequate method of contraception or birth control. For females of child bearing
potential, a negative pregnancy test within 7 days of start of study drug is required
- Prior cytotoxic therapy for metastatic or incurable disease.
- Patients may have had prior therapy with curative intent for localized disease, if
their recurrence or disease progression was more than six months from completing prior
- HER2 positive adenocarcinoma
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other
form of immunosuppressive therapy within 7 days prior to the first dose of trial
- Known history of active TB (Bacillus Tuberculosis)
- Known additional malignancy that is active. Exceptions include basal cell carcinoma of
the skin or squamous cell carcinoma of the skin that has undergone potentially
curative therapy or in situ cervical cancer.
- Previous invasive malignancy treated with curative intent less than 3 years from time
of registration. Exceptions include prostate cancer or basal cell skin cancer.
- Active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
- Known history of, or any evidence of active, non-infectious pneumonitis.
- Active infection requiring systemic therapy.
- History or current evidence of any condition, therapy, or laboratory abnormality that
might confound the results of the trial, interfere with the subject's participation
for the full duration of the trial, or is not in the best interest of the subject to
participate, in the opinion of the treating investigator.
- Known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
- Has received a live vaccine within 30 days of planned start of study therapy.