A Study of Nivolumab Combined With FOLFOX and Regorafenib in People Who Have HER2-Negative Esophagogastric Cancer

NCT04757363 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 20-540
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Esophagogastric Cancer; HER2-Negative

Keywords

nivolumab (OPDIVO®); regorafenib (STIVARGA®); fluorouracil; leucovorin; oxaliplatin; Regorafenib; esophageal cancer; 20-540

Outcome Measures

Primary Outcomes (1)

• 6-month progression free Survival

  will be defined according to RECIST 1.1.

  6 months

Study Arms (1)

Nivolumab Combined With FOLFOX and Regorafenib

EXPERIMENTAL

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).

Drug: regorafenib; Drug: nivolumab; Drug: FOLFOX chemotherapy with oxaliplatin

Interventions

regorafenib DRUG

regorafenib (80 mg on days 1-21 of the 28-day cycle)

Nivolumab Combined With FOLFOX and Regorafenib

nivolumab DRUG

nivolumab (240 mg on days 1 and 15 of the 28-day cycle).

Nivolumab Combined With FOLFOX and Regorafenib

FOLFOX chemotherapy with oxaliplatin DRUG

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).

Nivolumab Combined With FOLFOX and Regorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed metastatic esophageal, gastric, or gastroesophageal junction adenocarcinoma
• Patients must have disease that can be evaluated radiographically within 28 days of the start of study treatment. This may be measurable disease or non-measurable disease per RECIST 1.1.
• Age 18 years or older
• ECOG performance status 0 to 1
• Peripheral neuropathy grade ≤1
• Available archival tissue for correlative analysis (biopsy is required if no archival tissue is available)
• Adequate organ function as below:
• Absolute neutrophil count ≥1500/mcL
• Platelets ≥100,000/mcL
• Hemoglobin ≥9 g/dL
• Serum creatinine ≤1.5X ULN
• Serum total bilirubin ≤1.5X ULN OR Direct bilirubin ≤ULN for s ubjects with total bilirubin levels \>1.5X ULN, except patients with Gilbert's disease (≤3X ULN)
• AST and ALT ≤2.5X ULN
• Albumin ≥3 mg/dL
• ALT, alanine aminotransferase; AST, aminotransferase; ULN, upper limit of normal.

You may not qualify if:

• Confirmed HER2-positive disease (IHC 3+ or 2+, fluorescence in situ hybridization HER2:CEP17 ratio ≥2)
• ° Note: Participants that are IHC 2+ but negative by FSH w ill be considered HER2- negative and eligible for trial.
• Inability to swallow oral pills
• Prior chemotherapy for metastatic disease. Patients with metastatic disease after treatment for localized esophagogastric cancer may have received prior adjuvant therapy (chemotherapy and/or chemoradiation) if \>6 months have elapsed between the end of adjuvant therapy and registration
• Currently participating in a study and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Underwent major surgical procedure within 4 weeks of registration
• Underwent radiation within 2 weeks of registration
• Received prior therapy with regorafenib
• Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• 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
• A known history of active Bacillus tuberculosis
• A known active central nervous system metastases and/or carcinomatous meningitis
• A known history of or any evidence of active, noninfectious pneumonitis
• An active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, systemic lupus erythematosus, Wegener syndrome \[granulomatosis with polyangiitis\], myasthenia gravis, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis) within the 3 years before the start of treatment. The following are exceptions to this criterion:
• Subjects with vitiligo or alopecia

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Bayer: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (All Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (All Protocol Activities)

Uniondale, New York, 11553, United States

Location

Related Publications (1)

• Cytryn SL, Moy RH, Cowzer D, Shah RH, Chou JF, Joshi SS, Ku GY, Maron SB, Desai A, Yang J, Sugarman R, Rao D, Goldberg Z, Charalambous C, Lapshina M, Antoine A, Socolow F, Trivedi N, Capanu M, Gerdes H, Schattner MA, Simmons M, Lacouture ME, Paroder V, Tang LH, Shia J, Ilson DH, Solit DB, Berger MF, Janjigian YY. First-line regorafenib with nivolumab and chemotherapy in advanced oesophageal, gastric, or gastro-oesophageal junction cancer in the USA: a single-arm, single-centre, phase 2 trial. Lancet Oncol. 2023 Oct;24(10):1073-1082. doi: 10.1016/S1470-2045(23)00358-3. Epub 2023 Sep 1.

  PMID: 37666264 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

regorafenib; Nivolumab; Oxaliplatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals

Study Officials

• Yelena Janjigian, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-arm, open-label, nonrandomized, single-institution, phase II study of nivolumab in combination with FOLFOX and regorafenib as first-line therapy in patients with metastatic esophagogastric adenocarcinoma.

Study Record Dates

• First Submitted: February 12, 2021
• First Posted: February 17, 2021
• Study Start: February 11, 2021
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (7)