EGFR Monoclonal Antibody for Advanced Gastric Cancer

Phase 2

• Conditions: Nimotuzumab; Gastric Cancer; Cetuximab
• Interventions: Drug: EGFR antibody and Chemotherapy; Drug: Chemotherapy

• Registration Number: NCT04136600
• Lead Sponsor: Shanghai Changzheng Hospital

Brief Summary

This study is intended to evaluate efficacy and safety of EGFR monoclonal antibody (Cetuximab/Nimotuzumab) in combination with a chemotherapy in gastric cancer patients with EGFR amplification.

Detailed Description

This parallel, randomized, open-label, single-centre study will evaluate the effect on overall survival of EGFR monoclonal antibody (Cetuximab/Nimotuzumab) in combination with a chemotherapy compared to the chemotherapy alone in patients with EGFR-amplication advanced gastric cancer. Cetuximab will be administered as intravenous infusion of 500 mg/m2 (BSA) every 3 weeks, while nimotuzumab will be administered as intravenous infusion of 400mg every week. The chemotherapy consists of a combination of 12 cycles of mFOLFOX-6, 6-8 cycles of SOX, 6-8 cycles of CapOX. Treatment with cetuximab/nimotuzumab will continue until disease progression. The target sample size is 50-100 patients.

Study Timeline

• Study Start: 2019-07-01
• Study First Submitted: 2019-10-19
• Study First Submitted QC: 2019-10-22
• Study First Posted: 2019-10-23
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-28
• Last Update Posted: 2020-12-30
• Primary Completion: 2021-08-31
• Study Completion: 2021-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Adult patients >=18 years of age
• Inoperable locally advanced, recurrent, and/or metastatic cancer of the stomach or gastro-esophageal junction Adenocarcinoma
• EGFR-Amplification tumors (Copy Number>=5 for tissue or blood Next Generation Sequence)
• Expected survival ≥ 3 month;
• ECOG / PS score: 0-2;
• the main organ function to meet the following criteria: HB ≥ 90g / L, ANC ≥ 1.5 × 109 / L, PLT ≥ 80 × 109 / L,BIL <1.5 times the upper limit of normal (ULN); Liver ALT and AST <2.5 × ULN and if liver metastases, ALT and AST <5 × ULN; Serum Cr ≤ 1 × ULN, endogenous creatinine clearance ≥50ml/min;

Exclusion Criteria

• Previous chemotherapy for advanced/metastatic disease;
• Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome;
• History of cardiac disease;
• Dyspnoea at rest, due to complications of advanced malignancy or other disease, or patients who require supportive oxygen therapy;
• Patient can not comply with research program requirements or follow-up;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EGFR antibody arm	EGFR antibody and Chemotherapy	Participants received a dose of 500 mg/m2 Cetuximab iv on Day 1 of cycle every 3 weeks, or 400mg Nimotuzumab on Day 1 of cycle, every week, until disease progression. 12 cycles of mFOLFOX (5-fluorouracil (5-FU) 1,200 mg/m2/day for 46 hours, leucovorin 200 mg/m2, and oxaliplatin 85 mg/m2 biweekly). 6-8 cycles of CapOX (Xeloda, 1000 mg/m2 po twice daily for 14 days every 3 weeks + oxaliplatin 135mg/m2 every 3 weeks). 6-8 cycles of SOX (S-1, 60mg for BSA\>1.5, 50 mg for 1.5\>BSA\>1.25 , 40mg for BSA\<1.25 po twice daily for 14 days every 3 weeks + oxaliplatin 135mg/m2 every 3 weeks)
Placebo arm	Chemotherapy	12 cycles of mFOLFOX (5-fluorouracil (5-FU) 1,200 mg/m2/day for 46 hours, leucovorin 200 mg/m2, and oxaliplatin 85 mg/m2 biweekly). 6-8 cycles of CapOX (Xeloda, 1000 mg/m2 po twice daily for 14 days every 3 weeks + oxaliplatin 135mg/m2 every 3 weeks). 6-8 cycles of SOX (S-1, 60mg for BSA\>1.5, 50 mg for 1.5\>BSA\>1.25 , 40mg for BSA\<1.25 po twice daily for 14 days every 3 weeks + oxaliplatin 135mg/m2 every 3 weeks)

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	Evaluation of tumor burden until first documented progress through study completion, an average of 2 years	Time from treatment beginning until disease progression
Objective Response Rate	Evaluation of tumor burden through study completion, an average of 2 years	Proportion of patients with reduction in tumor burden of a predefined amount, including complete remission and partial remission.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	From date of treatment beginning until the date of death from any cause through study completion, an average of 2 years	Time from treatment beginning until death from any cause
Adverse Effect	Incidence of Treatment-related adverse Events through study completion, an average of 2 years	Incidence of Treatment-related adverse Events

Trial Locations

Locations (1)

Department of Medical Oncology, Shanghai Changzheng Hospital; 🇨🇳 Shanghai, China