NCT05677490 · Alliance for Clinical Trials in Oncology
mFOLFIRINOX Versus mFOLFOX With or Without Nivolumab for the Treatment of Advanced, Unresectable, or Metastatic HER2 Negative Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma
What this study is about
This phase III trial compares the effect of modified fluorouracil, leucovorin calcium, oxaliplatin, and irinotecan (mFOLFIRINOX) to modified fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX) for the treatment of advanced, unresectable, or metastatic HER2 negative esophageal, gastroesophageal junction, and gastric adenocarcinoma.
View original scientific description
This phase III trial compares the effect of modified fluorouracil, leucovorin calcium, oxaliplatin, and irinotecan (mFOLFIRINOX) to modified fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX) for the treatment of advanced, unresectable, or metastatic HER2 negative esophageal, gastroesophageal junction, and gastric adenocarcinoma. The usual approach for patients is treatment with FOLFOX chemotherapy.
Interventions
DRUG
Fluorouracil
Given IV
DRUG
Leucovorin Calcium
Given IV
DRUG
Oxaliplatin
Given IV
DRUG
Irinotecan
Given IV
BIOLOGICAL
Nivolumab
Given IV
PROCEDURE
Magnetic Resonance Imaging
Undergo MRI
PROCEDURE
Computed Tomography
Undergo a CT Scan
PROCEDURE
Biospecimen Collection
Undergo blood sample collection
OTHER
Questionnaire Administration
Ancillary studies
Primary outcome measures
Overall survival (OS)
Time frame: 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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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
Where
- Birmingham, Alabama
- Anchorage, Alaska
- Fairbanks, Alaska
- Kingman, Arizona
- Phoenix, Arizona
- Fort Smith, Arkansas
- Little Rock, Arkansas
- Antioch, California
- Arroyo Grande, California
- Auburn, California
- Berkeley, California
- Burbank, California
And 496 more locations — see the full list below.
Collaborators
National Cancer Institute (NCI)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jul 2, 2026 · Source of record for eligibility and locations