EGFR Monoclonal Antibody for Advanced Gastric Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Study of EGFR Monoclonal Antibody (Cetuximab/Nimotuzumab) in Combination With Chemotherapy Compared With Chemotherapy Alone in Patients With EGFR-amplification Advanced Gastric Cancer

Conditions
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Gastric Cancer, Cetuximab, Nimotuzumab

Intervention / Treatment
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* Drug: EGFR antibody and Chemotherapy
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EGFR antibody arm<br>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) | Drug: EGFR antibody and Chemotherapy<br>* Drug: Cetuximab Cetuximab: 500 mg/m2 iv on Day 1 of cycle every 3 weeks, until disease progression. Other Names: Erbitux Drug: Nimotuzumab Nimotuzumab: 400mg iv on Day 1 of cycle, every week, until disease progression Drug: Fluoropyrimidine 5-fluorouracil (5-FU): 2,400 mg/m2/day iv in first 46 hours of cycle, every two weeks for 12 cycles Other Names: 5-Fu Drug: Capecitabine Capecitabine: 1000 mg/m2 po twice daily for 14 days every 3 weeks, for 6 cycles Other Names: Xeloda Drug: S-1 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, for 6 cycles Other Names: S-1 Drug: Oxaliplatin Oxaliplatin: 85 mg/m2 iv on Day 1 of cycle, every 2 week for 12 cycles with 5-Fu; Oxaplatin: 130 mg/m2 iv on Day 1 of cycle, every 3 week for 6 cycles combined with S-1 or Capecitabine;<br>|
| Placebo Comparator: Placebo arm<br>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) | Drug: Chemotherapy<br>* Drug: Fluoropyrimidine 5-fluorouracil (5-FU): 2,400 mg/m2/day iv in first 46 hours of cycle, every two weeks for 12 cycles Other Names: 5-Fu Drug: Capecitabine Capecitabine: 1000 mg/m2 po twice daily for 14 days every 3 weeks, for 6 cycles Other Names: Xeloda Drug: S-1 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, for 6 cycles Other Names: S-1 Drug: Oxaliplatin Oxaliplatin: 85 mg/m2 iv on Day 1 of cycle, every 2 week for 12 cycles with 5-Fu; Oxaplatin: 130 mg/m2 iv on Day 1 of cycle, every 3 week for 6 cycles combined with S-1 or Capecitabine;<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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