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Comparing two chemotherapy regimens for advanced HER2 negative gastric and esophageal cancer

Randomized Phase III Trial of mFOLFIRINOX vs. FOLFOX With Nivolumab for First-Line Treatment of Metastatic HER2- Gastroesophageal Adenocarcinoma

Phase 3 Interventional Alliance for Clinical Trials in Oncology · NCT05677490

This study is testing if a new chemotherapy combination can help people with advanced HER2 negative stomach and esophageal cancer live longer compared to the standard treatment.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment382 (estimated)
Ages18 Years and up
SexAll
SponsorAlliance for Clinical Trials in Oncology Academic / other
Drugs / interventionsnivolumab, chemotherapy, immunotherapy, prednisone
Locations792 sites (Birmingham, Alabama and 791 other locations)
Trial IDNCT05677490 on ClinicalTrials.gov

What this trial studies

This phase III trial evaluates the effectiveness of modified FOLFIRINOX versus modified FOLFOX, with or without the addition of nivolumab, in treating advanced, unresectable, or metastatic HER2 negative esophageal, gastroesophageal junction, and gastric adenocarcinoma. The study aims to determine if the mFOLFIRINOX regimen improves overall survival compared to the standard FOLFOX treatment. Secondary objectives include assessing progression-free survival, response rates, safety, and tolerability of the treatments. Patients will be randomized into two arms to receive either chemotherapy regimen, with some also receiving immunotherapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with unresectable or metastatic HER2 negative adenocarcinoma of the esophagus, gastroesophageal junction, or stomach.

Not a fit: Patients with prior treatment for unresectable or metastatic disease or those with HER2 positive tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for patients with advanced HER2 negative gastric and esophageal cancers.

How similar studies have performed: Other studies have shown promising results with similar chemotherapy and immunotherapy combinations, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* 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 Criteria:

* Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects

  \* Therefore, for women of childbearing potential only, a negative serum or urine pregnancy test done =\< 7 days prior to registration is required
* 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

Where this trial is running

Birmingham, Alabama and 791 other locations

+742 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Advanced Esophageal AdenocarcinomaAdvanced Gastric AdenocarcinomaAdvanced Gastroesophageal Junction AdenocarcinomaClinical Stage III Esophageal Adenocarcinoma AJCC v8Clinical Stage III Gastric Cancer AJCC v8Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8Clinical Stage IV Esophageal Adenocarcinoma AJCC v8Clinical Stage IV Gastric Cancer AJCC v8
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.