Neoadjuvant Bev Plus DOF vs DOF in LAGC and Its Association With Circulating Tumor Cell

Study Overview
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Brief Summary
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Background Local advanced gastric carcinoma (LAGC) is suggested to be potentially cured by R0 resection, and neoadjuvant chemotherapy can increase the R0 resection rate but not enough. Bevacizumab (Bev), an anti-tumor angiogenesis monoclonal antibody, combined with chemotherapy has been shown effective in advanced GC. In addition, CTC has been suggested as an indicator of the anti-tumor drugs' efficacy. Therefore, in this study, the investigators plan to evaluate the efficacy and safety of neoadjuvant Bev plus docetaxel/oxaliplatin/5-FU/CF (DOF) versus DOF in mainly gastric antrum LAGC, and to investigate whether CTC is an effectiveness indicator. Methods 86 patients diagnosed as IIIb-IIIc GC have been enrolled and randomly assigned (1:1) to receive neoadjuvant Bev (5 mg/kg, d1) plus DOF (docetaxel, 75 mg/m2, iv, d1; oxaliplatin, 85 mg/m2, iv, d1; 5-FU, iv infusion 600 mg/m2 and iv injection 400mg/m2, d1-2; CF, 200 mg/m2, d1 and d2) or DOF each 3-week, up to 2-4 cycles preoperation, and another 2-4 cycles postoperation up to total 6 cycles. The primary endpoint is R0 resection rate. CTC was detected every 8 weeks. All patients signed the informed consent.

Official Title
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Phase 2 Study of Neoadjuvant Bevacizumab Plus DOF Versus DOF in Local Advanced Gastric Carcinoma and Its Association With Circulating Tumor Cell

Conditions
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Locally Advanced Gastric Carcinoma

Intervention / Treatment
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* Biological: Bevacizumab
* Drug: docetaxel oxaliplatin 5-FU CF
* Procedure: Gastrectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed locally advanced adenocarcinoma of the stomach. Age of 18 to 70, Karnofsky score higher than 80. T3-4，N1-3，M0 (AJCC 7th), potentially resectable. No severe functional damage of major organ, normal blood cell, normal liver and kidney function. Exclusion Criteria: Clinical findings of distant metastasis or Peritoneal carcinomatosis Prior systemic (chemo- or targeted) treatment. Prior radiotherapy to the upper abdomen Previous malignancy within 5 years, with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer Upper gastrointestinal bleeding Any contraindication to treatment with docetaxel, 5-fu or oxaliplatin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bevacizumab plus DOF<br>patients receive bev +DOF pre and post surgery up to total 6 cycles | Biological: Bevacizumab<br>* Bev (5 mg/kg, d1) every 3 weeks, up to 2-4 cycles preoperation, and another 2-4 cycles postoperation up to total 6 cycles.<br>Drug: docetaxel oxaliplatin 5-FU CF<br>* docetaxel, 75 mg/m2, iv, d1; oxaliplatin, 85 mg/m2, iv, d1; 5-FU, iv infusion 600 mg/m2 and iv injection 400mg/m2, d1-2; CF, 200 mg/m2, d1 and d2 each 3-week, up to 2-4 cycles preoperation, and another 2-4 cycles postoperation up to total 6 cycles.<br>Procedure: Gastrectomy<br> <br> |
| Active Comparator: DOF<br>patients receive DOF pre and post surgery up to total 6 cycles | Drug: docetaxel oxaliplatin 5-FU CF<br>* docetaxel, 75 mg/m2, iv, d1; oxaliplatin, 85 mg/m2, iv, d1; 5-FU, iv infusion 600 mg/m2 and iv injection 400mg/m2, d1-2; CF, 200 mg/m2, d1 and d2 each 3-week, up to 2-4 cycles preoperation, and another 2-4 cycles postoperation up to total 6 cycles.<br>Procedure: Gastrectomy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 resection rate |  | 6-12 weeks after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pCR rate |  | Day 1 after surgery | 
| OS |  | 3 years after surgery | 
| DFS |  | 3 years after surgery | 
| ORR |  | 6 weeks after administration | 
| safety of peroperative treatment and surgery |  | from first administration to 28 days after last administration |