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Study of Chemotherapy with or without Nivolumab for Advanced Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma

This study is comparing two chemotherapy combinations, mFOLFIRINOX and mFOLFOX, with or without the immunotherapy drug nivolumab, for advanced, unresectable (cannot be surgically removed), or metastatic (spread to other parts of the body) HER2-negative esophageal, gastroesophageal junction, and gastric adenocarcinoma. The study aims to see if mFOLFIRINOX, with or without nivolumab, improves how long people live compared to mFOLFOX, with or without nivolumab. You may be eligible if you are 18 or older, have HER2-negative adenocarcinoma, and your tumor's PD-L1 status is known. The study plans to enroll 382 participants.

Study design
This is an interventional study that will randomize participants into different treatment groups. It plans to enroll 382 participants.
What's involved
Not specified in the trial record.
Compensation
Not stated in the trial record.
Follow-up
Your overall survival will be measured for up to 2 years from the time you are assigned to a treatment group.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT05677490

mFOLFIRINOX Versus mFOLFOX With or Without Nivolumab for the Treatment of Advanced, Unresectable, or Metastatic HER2 Negative Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma

Recruiting
PHASE3Ages 18+InterventionalTreatment
Alliance for Clinical Trials in Oncology
~382 participants
Updated 2026-08-05 on ClinicalTrials.gov
What's tested:FluorouracilLeucovorin CalciumOxaliplatinIrinotecanNivolumabMagnetic Resonance Imaging

At a glance

Recruiting sites
633 of 793 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Overall survival (OS)
Measured over Up to 2 years from the time of randomization.

Conditions

Advanced Esophageal Adenocarcinoma
Advanced Gastric Adenocarcinoma
Advanced Gastroesophageal Junction Adenocarcinoma
Clinical Stage III Esophageal Adenocarcinoma AJCC v8
Clinical Stage III Gastric Cancer AJCC v8
Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8
Clinical Stage IV Esophageal Adenocarcinoma AJCC v8
Clinical Stage IV Gastric Cancer AJCC v8
Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8
Metastatic Esophageal Adenocarcinoma
Metastatic Gastric Adenocarcinoma
Metastatic Gastroesophageal Junction Adenocarcinoma
Unresectable Esophageal Adenocarcinoma
Unresectable Gastric Adenocarcinoma
Unresectable Gastroesophageal Junction Adenocarcinoma

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Where it's being run

793 sites across 48 states
California80
Michigan70
Ohio67
Illinois59
Minnesota53
Wisconsin52
Colorado47
Nevada41

Who to contact

Aishwarya Vijendran
[email protected]
773-834-9613
Email the study team

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

Histologic documentation: HER2 negative adenocarcinoma as defined by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines (Bartley et al., Journal of Clinical Oncology \[JCO\] 2017) with known PD-L1 CPS (Any CPS is allowed, but should be known prior to registration)
Stage: unresectable or metastatic
Tumor site: esophagus, gastroesophageal junction, or stomach
Measurable disease or non-measurable but evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
No prior treatment for unresectable or metastatic disease
Prior neoadjuvant or adjuvant cytotoxic chemotherapy or adjuvant immunotherapy is allowed as long as it was completed at least 1 year prior to registration
Age \>= 18 years
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
Absolute neutrophil count (ANC) \>= 1,500/mm\^3
Platelet count \>= 100,000/mm\^3
Creatinine =\< 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance \>= 30 mL/min
Total bilirubin =\< 1.5 x ULN
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x ULN (in patients with liver metastasis: =\< 5 x ULN if clearly attributable to liver metastases)
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Patients positive for human immunodeficiency virus (HIV) are eligible only if they meet all of the following:
On effective anti-retroviral therapy
Undetectable HIV viral load by standard clinical assay =\< 6 months of registration
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
Patients who will receive nivolumab in addition to chemotherapy must not have any contraindications to immune checkpoint inhibitors
Patients must not have active autoimmune disease that has required systemic treatment within 6 months prior to registration. Patients are permitted to receive immunotherapy if they have vitiligo, type I diabetes, 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)
Patients must not have a condition requiring systemic treatment with either corticosteroids (\>10mg/day prednisone equivalents) or other immunosuppressive medications within 14 days prior to registration. Inhaled or topical steroids and adrenal replacement doses (=\< 10mg/day prednisone equivalent) are permitted
Patients must not have a history of noninfectious pneumonitis requiring steroids
Patients with prior immune mediated adverse events related to immunotherapy that resulted in permanent treatment discontinuation with these agents are ineligible
This study includes the use of the mandatory patient completed measure, PRO-CTCAE. For this study the PRO-CTCAE is available in English, Spanish, Korean, Chinese (Simplified), and Russian, hence patients must be able to speak, understand and read in these languages. Ad-hoc translation of patient-reported measures is not permitted

Exclusion

Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
No known Gilbert's syndrome or known homozygosity for UGAT1A1\*28 polymorphism
No baseline grade \>= 2 peripheral neuropathy, neurosensory toxicity, or neuromotor toxicity per CTCAE version (v) 5.0 regardless of causality
No medical condition such as uncontrolled infection or uncontrolled diabetes mellitus which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
No untreated, symptomatic brain metastasis. Patients with treated brain metastases are eligible if the following criteria are met: 1) follow-up brain imaging done at least in 4 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression and 2) the patient no longer requires steroids, or is on a stable steroid dose for more than four weeks
No allogeneic tissue/organ transplant

What this trial measures

  • Overall survival (OS)Up to 2 years from the time of randomization.

    Will compare the distributions of OS between the two treatment arms to determine if patients treated with modified fluorouracil, leucovorin calcium, oxaliplatin, and irinotecan (mFOLFIRINOX) (with or without nivolumab) have an OS benefit compared to those treated with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) (with or without nivolumab). Kaplan-Meier methodology will be used to estimate the distributions for the treatment arms. To compare the OS distributions between the two treatment arms, we will use a one-sided logrank test to evaluate if mFOLFIRINOX (with or without nivolumab) is superior to mFOLFOX (with or without nivolumab) based on an intention to treat analysis. The hazard ratio, median OS, and estimated OS rates at 1 and 2 years will be estimated along with corresponding 95% confidence intervals. Multivariable Cox proportional hazards models will also be used to assess the impact of treatment arm on OS when stratifying on the stratification factors.