EGFR Monoclonal Antibody for Advanced Gastric Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: EGFR antibody arm 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
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;
|
| Placebo Comparator: Placebo arm 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
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;
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Adult patients >=18 years of age
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Inoperable locally advanced, recurrent, and/or metastatic cancer of the stomach or gastro-esophageal junction Adenocarcinoma
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EGFR-Amplification tumors (Copy Number>=5 for tissue or blood Next Generation Sequence)
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Expected survival ≥ 3 month;
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ECOG / PS score: 0-2;
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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:
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Previous chemotherapy for advanced/metastatic disease;
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Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome;
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History of cardiac disease;
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Dyspnoea at rest, due to complications of advanced malignancy or other disease, or patients who require supportive oxygen therapy;
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Patient can not comply with research program requirements or follow-up;
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Medical Oncology, Shanghai Changzheng Hospital | Shanghai | China |
Sponsors and Collaborators
- Shanghai Changzheng Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EGFR-GC