Nivolumab + FOLFOX + Regorafenib for Esophageal Cancer

Recruiting in Palo Alto (17 mi)

+6 other locations

Overseen byYelena Janjigian, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Memorial Sloan Kettering Cancer Center

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?The purpose of this study is to find out whether combining nivolumab, FOLFOX, and regorafenib may be a safe and effective treatment for people who have HER2-negative metastatic esophagogastric cancer. Nivolumab is an antibody, like the proteins made by the immune system to protect the body from harm. Nivolumab blocks the protein PD-1 (programmed cell death receptor-1) that usually acts as a "brake" on the immune system. Blocking this protein is like releasing the brakes, so that the immune system can target cancer cells and destroy them. FOLFOX is a combination of three standard chemotherapy drugs (leucovorin, 5-fluorouracil, and oxaliplatin) commonly used to treat your type of cancer. The drugs work by damaging the DNA in cancer cells, which can cause the cells to stop growing and die. Regorafenib is a type of drug called a tyrosine kinase inhibitor (TKI). This drug targets the tyrosine kinase protein found in or on the surface of cancer cells that the cells need to survive and grow. Blocking this protein may stop cancer cells from growing, or cause them to grow more slowly or to shrink. The study researchers think that combining nivolumab, FOLFOX, and regorafenib may be a more effective treatment for HER2-negative metastatic esophagogastric cancer than the usual chemotherapy treatment(s) alone.

Eligibility Criteria

Adults with HER2-negative metastatic esophagogastric cancer can join this trial. They should have adequate organ function, no severe neuropathy, and their disease must be visible on scans. Excluded are those with HER2-positive cancer, difficulty swallowing pills, recent major surgery or radiation, prior regorafenib treatment, certain autoimmune diseases unless specified exceptions apply, active infections like HIV or hepatitis B/C, uncontrolled heart conditions or blood pressure issues.

Inclusion Criteria

AST and ALT ≤2.5X ULN

Absolute neutrophil count ≥1500/mcL

Platelets ≥100,000/mcL

+18 more

Exclusion Criteria

Diagnosis of immunodeficiency or receipt of systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of trial treatment

You are unable to swallow pills.

You have already received treatment with regorafenib.

+21 more

Participant Groups

The study is testing a combination of nivolumab (an immune system booster), FOLFOX chemotherapy (a DNA-damaging drug trio), and regorafenib (a growth-blocking drug) to see if they work better together than standard treatments for advanced stomach cancers that don't respond to HER2-targeted therapies.

1Treatment groups

Experimental Treatment

Group I: Nivolumab Combined With FOLFOX and RegorafenibExperimental Treatment3 Interventions

Each treatment cycle consists of 28 days. Patients will initially receive induction therapy with regorafenib (80 mg on days 1-21 of the 28-day cycle) and nivolumab (240 mg on days 1 and 15 of the 28-day cycle). Starting on cycle 2, day 1, patients will also receive FOLFOX chemotherapy with oxaliplatin (85 mg/m2 IV), leucovorin (400 mg/m2 IV), 5-FU (400 mg/m2 IV bolus), and 5-FU (2400 mg/m2/day continuous IV infusion over 48 h). If the patient is not a good candidate for induction regorafenib and nivolumab (i.e. symptomatic from a large burden of disease), 5-FU and oxaliplatin can be added during cycle 1 at the treating physician's discretion. 39 Patients will continue with this regimen until disease progression, unacceptable toxicity, or development of serious intercurrent illness. Treatment will be performed on the scheduled day (±7-day treatment window).