Futibatinib With Paclitaxel and Ramucirumab for the Treatment of Locally Advanced or Unresectable Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma

NCT07594548 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: NU 25I08NCI-2026-03370STU00225647P30CA060553
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial tests the safety, side effects and best dose of futibatinib with paclitaxel and ramucirumab for the treatment of patients with gastric, gastroesophageal junction or esophageal adenocarcinoma that has spread to nearby tissue or lymph nodes (locally advanced) or that cannot be removed by surgery (unresectable). Futibatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Giving futibatinib with paclitaxel and ramucirumab may be safe and tolerable in treating patients with locally advanced or unresectable gastric, gastroesophageal junction or esophageal adenocarcinoma.

Conditions

Clinical Stage III Esophageal Adenocarcinoma AJCC v8; Clinical Stage IV Esophageal Adenocarcinoma AJCC v8; Clinical Stage IV Gastric Cancer AJCC v8; Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Locally Advanced Esophageal Adenocarcinoma; Locally Advanced Gastric Adenocarcinoma; Locally Advanced Gastroesophageal Junction Adenocarcinoma; Metastatic Esophageal Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Unresectable Esophageal Adenocarcinoma; Clinical Stage III Gastric Cancer AJCC v8; Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Metastatic Gastroesophageal Junction Adenocarcinoma; Unresectable Gastric Adenocarcinoma; Clinical Stage II Esophageal Adenocarcinoma AJCC v8; Unresectable Gastroesophageal Junction Carcinoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose

  Defined as the highest dose that causes dose-limiting toxicities (DLTs) in \< 2 of 6 subjects. Will be estimated using the Bayesian Optimal Interval algorithm based on observed DLTs. The frequency of DLTs at each dose level will be summarized using descriptive statistics, including proportions and confidence intervals.

  From cycles 1 day 8 (start of Futibatinib) to cycle 2 day 8 (cycle length = 28 days)

• Recommended phase 2 dose

  Up to 2 years

Secondary Outcomes (5)

• Incidence of adverse events

  Up to 2 years

• Objective response rate

  From treatment initiation until the response has been confirmed, the patient experiences disease progression, initiates subsequent anti-cancer therapy, or completes study participation, up to 2 years after completion of study treatment

• Duration of response (DOR)

  From the first scan showing CR or PR to disease progression or death, up to 2 years after completion of study treatment

• Progression free survival (PFS)

  From treatment initiation and the earlier of the day of first documented disease progression or death, up to 2 years after completion of study treatment

• Overall survival (OS)

  From start of treatment and the date of death from any cause, up to 2 years after completion of study treatment

Study Arms (1)

Treatment (futibatinib, paclitaxel, ramucirumab)

EXPERIMENTAL

Patients receive ramucirumab IV over 30-60 minutes on days 1 and 15 of each cycle, paclitaxel IV over 60 minutes on days 1, 8 and 15 of each cycle, and futibatinib PO QD on days 8-28 of cycle 1 and days 1-28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI, and optional blood and urine sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Futibatinib; Procedure: Magnetic Resonance Imaging; Drug: Paclitaxel; Biological: Ramucirumab

Interventions

Biospecimen Collection PROCEDURE

Undergo blood and urine sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (futibatinib, paclitaxel, ramucirumab)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (futibatinib, paclitaxel, ramucirumab)

Futibatinib DRUG

Given PO

Also known as: Lytgobi, TAS 120, TAS-120, TAS120

Treatment (futibatinib, paclitaxel, ramucirumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (futibatinib, paclitaxel, ramucirumab)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (futibatinib, paclitaxel, ramucirumab)

Ramucirumab BIOLOGICAL

Given IV

Also known as: Anti-VEGFR-2 Fully Human Monoclonal Antibody IMC-1121B, Cyramza, IMC 1121B, IMC-1121B, IMC1121B, LY 3009806, LY-3009806, LY3009806, Monoclonal Antibody HGS-ETR2

Treatment (futibatinib, paclitaxel, ramucirumab)

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 locally advanced/unresectable gastric, gastroesophageal junction, or esophageal adenocarcinoma that is microsatellite stable and HER2 negative. (American Joint Committee on Cancer \[AJCC\] staging criteria; https://pmc.ncbi.nlm.nih.gov/articles/PMC5387145/)
• Note: Histological or cytological test reports from external laboratories outside of Northwestern University (NU) will also be accepted
• Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Note: Patients must have documented unresectable and/or metastatic disease on CT or MRI imaging completed prior to registration. Imaging must have been completed within 90 days prior to registration for participants with measurable disease
• Patients must not have received more than 1 prior line of therapy in the metastatic setting.
• Note: Patients who have received neoadjuvant or adjuvant therapy must have completed therapy a year prior to registration in this study. Exception: patients with neoadjuvant or adjuvant therapy who have progressed within 6 months
• Patients must be age ≥ 18 years
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Leukocytes (white blood cells \[WBC\]) ≥ 2,000/mcL
• Absolute neutrophil count (ANC) ≥ 1500/mcL
• Hemoglobin (Hgb) ≥ 9 g/dL (transfusions within 1 week of registration are not allowed to meet cutoff)
• Platelets (PLT) ≥ 100,000/mcL (transfusions within 1 week of registration are not allowed to meet cutoff)
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) ≤ 3 x institutional ULN (unless liver metastases are present, in which case they must be ≤ 5 x ULN)
• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN (unless liver metastases are present, in which case they must be ≤ 5 x ULN)

You may not qualify if:

• Patients with adenosquamous or mixed histology disease
• Patients who have received/are receiving other investigational agents, or anticancer/antineoplastic therapy including chemotherapy, immunotherapy, biological response modifiers, anti-neoplastic endocrine therapy or devices concurrently or within 21 days or 5 times the half-life, whichever is shorter, prior to first dose of cycle 1
• Patients who have previously received a FGFR inhibitor.
• Note: Agents that are multi-kinase inhibitors are allowed
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia, neuropathy and other non-significant adverse events per NCI CTCAE v 6.0
• Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel, ramucirumab, or futibatinib
• Patients who have major surgical procedure planned during the study or any surgery within 28 days of registration or any subcutaneous venous access device placement within 7 days prior registration
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, or who have experienced arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to registration ,should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.
• Note: To be eligible for this trial, patients should be class 2B or better
• History of gastrointestinal perforation and/or fistulae within 6 months prior to registration
• History of active bleeding or significant gastrointestinal (GI) bleeding requiring intervention within 60 days prior to registration
• History and/or current evidence of endocrine alteration of calcium-phosphorus homeostasis. History and/or current evidence of ectopic mineralization/calcification including but not limited to soft tissue, kidneys, intestine, or myocardia and lung with the exception of calcified lymph nodes and asymptomatic arterial calcification
• Current evidence of retinal disorder/keratopathy including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis, etc., confirmed by ophthalmologic examination
• Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following:
• Hypertension that is not controlled on medication(per treating physician's discretion)

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• Northwestern University: lead

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Interventions

Specimen Handling; futibatinib; Magnetic Resonance Spectroscopy; Paclitaxel; Taxes; Ramucirumab

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Chengwei Peng, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Coordinator

CONTACT

3126951301; cancer@northwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2026
• First Posted: May 18, 2026
• Study Start (Estimated): September 9, 2027
• Primary Completion (Estimated): September 9, 2030
• Study Completion (Estimated): September 9, 2031
• Last Updated: May 18, 2026

Record last verified: 2026-05

Locations

US (2)