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

Cancer Categories

Gastrointestinal (GI)

Karmanos Trial ID

A022102

NCT ID

NCT05677490

Age Group

Adult

Scope

National

Phase

Phase III

Principal Investigator

Mohammed Najeeb
Al Hallak, M.D., MS
Oncology - Medical View Profile

Objective:

Primary Objective:

To determine if overall survival (OS) is improved in patients who received mFOLFIRINOX +/- nivolumab in comparison to FOLFOX +/- nivolumab as first-line chemotherapy for metastatic gastroesophageal adenocarcinoma.

Secondary Objectives:

To compare other indices of efficacy, including progression-free survival, objective response rates and duration of response between both treatment arms
To evaluate safety and tolerability associated with treatment in each of the treatment arms
To evaluate the proportion of patients receiving second line of therapy in both arms
To evaluate tolerability of the treatment in both arms using PRO-CTCAE

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Eligibility

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

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