Actively Recruiting
A Phase II Study of Neratinib Combined with Chemotherapy, Trastuzumab, and Pembrolizumab in HER2 Overexpressing Gastroesophageal Cancers
Led by H. Lee Moffitt Cancer Center and Research Institute · Updated on 2026-02-09
36
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
Sponsors
H
H. Lee Moffitt Cancer Center and Research Institute
Lead Sponsor
P
Puma Biotechnology, Inc.
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the effects and safety of the drug Neratinib combined with Trastuzumab, Pembrolizumab, and FOLFOX chemotherapy in patients with HER2 overexpressing gastroesophageal cancers, including esophageal, gastric, and gastroesophageal junction adenocarcinoma. This phase II study aims to understand both the benefits and potential risks of this combination treatment in this specific cancer type. All participants will receive Neratinib orally at 240 mg daily, Trastuzumab and chemotherapy (5-Fluorouracil, leucovorin, and Oxaliplatin) intravenously every two weeks, and Pembrolizumab intravenously every six weeks. The chemotherapy and Trastuzumab dosing follow standard schedules, with Pembrolizumab given every third cycle. This combined treatment approach is given throughout the study period. Participants will be monitored for up to 24 months, with researchers assessing tumor response using the Objective Response Rate and other measures like Clinical Benefit Rate, Duration of Response, and Overall Survival. Safety is closely observed, including heart function and other organ functions. Patients will undergo regular imaging, laboratory tests, and clinical evaluations to track treatment effects and side effects during the study.
CONDITIONS
Brief Title
Neratinib In Combination With Chemotherapy/Trastuzumab/Pembrolizumab In HER2 Gastroesophageal Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients must have confirmed esophageal, gastric, or gastroesophageal junction adenocarcinoma.
- HER2 overexpression or amplification must be confirmed by recent testing.
- No prior chemotherapy for stage IV disease or treatment-naïve for metastatic disease.
- Measurable disease by RECIST v1.1 criteria.
- Normal or acceptable heart function (LVEF ≥ 53%; borderline LVEF 40-52% considered after cardiology review).
- ECOG performance status 0 or 1.
- Adequate organ function as per protocol.
- Female patients of childbearing potential must have negative pregnancy test and agree to use two birth control methods or be surgically sterile.
- Male patients must agree to use contraception during and after the study.
- Patients with treated brain metastases are eligible if stable after treatment.
- Ability and willingness to provide informed consent.
You will not qualify if you...
- Participation in another investigational study or treatment within 4 weeks prior to study start.
- Prior chemotherapy, targeted therapy, or immunotherapy for metastatic disease unless recovered from side effects.
- Active central nervous system metastases or carcinomatous meningitis.
- Active autoimmune disease requiring systemic therapy in past 2 years.
- Immunodeficiency or chronic steroid therapy above prednisone 10 mg/day equivalent.
- History or current pneumonitis requiring steroids.
- Active infection needing systemic treatment.
- Baseline peripheral neuropathy greater than grade 1.
- Significant medical or psychiatric conditions interfering with study participation.
- Pregnancy, breastfeeding, or planning pregnancy during study period.
- COVID-19 infection within 90 days or ongoing symptoms.
- Significant cardiac disease including congestive heart failure NYHA class > II, active coronary artery disease, arrhythmias needing certain treatments, unstable angina, recent myocardial infarction, or prolonged QTc.
- Chronic gastrointestinal disorders with diarrhea as major symptom or grade ≥2 diarrhea at screening.
AI-Screening
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Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 24 months
Participants receive a combination of neratinib daily by mouth, trastuzumab and chemotherapy every 2 weeks, and pembrolizumab every 6 weeks as part of their cancer treatment.
Biweekly visits for trastuzumab and chemotherapy; pembrolizumab given every 6 weeks; daily oral neratinib
Trial Site Locations
Total: 1 location
1
Moffitt Cancer Center
Tampa, Florida, United States, 33612
Actively Recruiting
Research Team
E
Erin Mcewan
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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