Phase II Study of Short Course FOLFOX Chemotherapy With Either Nivolumab or Nivolumab + Radiation in the First Line Treatment of Metastatic or Unresectable Gastroesophageal Cancers (BMS Protocol CA209-76L)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Gastroesophageal Adenocarcinoma
• Intervention / Treatment: Drug: Nivolumab 240 MG

Detailed Description

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 February 2026.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • University of Nebraska
  • New York
    • Buffalo, New York, United States, 14203
      • Roswell Park Cancer Center
    • New York, New York, United States, 10065
      • Weill Cornell Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• 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 disease.
• 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

Exclusion Criteria

• 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 therapy.
• 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 treatment.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort 1; Subjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 1 will receive Nivolumab alone (every 2 weeks for two doses, and then every 4 weeks)	Drug: Nivolumab 240 MG; Nivolumab (OpdivoTM) is a potent and highly selective humanized monoclonal antibody (mAB) designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Cancer cells are able to send a signal to the PD-1 via the PD-L1 molecule, tricking the T-cell into recognizing the cancer cell as normal. Nivolumab is designed to disrupt that signal and expose the cancer cell to the immune system. Nivolumab is given intravenously over a 60-minute period, usually every two weeks.
Experimental: Cohort 2; Subjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 2 will receive Nivolumab (every 2 weeks for two doses, and then every 4 weeks) plus radiation therapy (total 5 sessions)	Drug: Nivolumab 240 MG; Nivolumab (OpdivoTM) is a potent and highly selective humanized monoclonal antibody (mAB) designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Cancer cells are able to send a signal to the PD-1 via the PD-L1 molecule, tricking the T-cell into recognizing the cancer cell as normal. Nivolumab is designed to disrupt that signal and expose the cancer cell to the immune system. Nivolumab is given intravenously over a 60-minute period, usually every two weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with 12-month progression free survival	This will be measured by number of patients without disease progression at 12 months in the two study arms (patients who receive nivolumab with radiation and those who receive nivolumab alone)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects who receive short course chemotherapy with immunotherapy that achieve 12-month progression free survival	This will be measured by the number of patients without disease progression at 12 months in all enrolled patients.	12 months
Overall Survival, as measured by the rate of survival in patients	In both study arms, and in all patients together, we will examine the rate of survival in patients over time from registration through their treatment	2 year
Occurrence of Significant Toxicity, as measured by Number of Grade 3 and Grade 4 Adverse Events (Combined) Attributable to Immunotherapy	We will measure the rate of grade 3 or 4 adverse events attributable to immunotherapy in both study arms	2 year

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Manish Shah, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2019
• Primary Completion (Actual): June 11, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: July 12, 2019
• First Submitted That Met QC Criteria: July 12, 2019
• First Posted (Actual): July 16, 2019

Study Record Updates

• Last Update Posted (Actual): June 24, 2025
• Last Update Submitted That Met QC Criteria: June 20, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Nivolumab
• Other Study ID Numbers: 1812019872

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No