Efficacy of Docetaxel, Capecitabine, Cisplatin, and Bevacizumab in Patients With Unresectable Advanced Gastric Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine whether docetaxel, capecitabine, cisplatin, and bevacizumab are effective in the treatment of unresectable advanced gastric cancer.

Detailed Description
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In our previous phase II study of neoadjuvant docetaxel, capecitabine and cisplatin chemotherapy, patients with unresectable gastric cancer because of invasion to adjacent organs or metastasis to para-aortic lymph nodes received benefit from neoadjuvant chemotherapy. Based on these results and reports that bevacizumab enhances response rate, we planned docetaxel, capecitabine, cisplatin, and bevacizumab as neoadjuvant chemotherapy for patients with local invasion or para-aortic node metastasis alone.

Official Title
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A Phase II Study of Neoadjuvant Chemotherapy With Docetaxel, Capecitabine, Cisplatin, and Bevacizumab in Patients With Unresectable Advanced Gastric Cancer

Conditions
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Advanced Gastric Cancer

Intervention / Treatment
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* Drug: Docetaxel, Capecitabine, Cisplatin, Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically documented adenocarcinoma of the stomach or gastroesophageal junction. Invasion to adjacent organ (T4) proven by endoscopic ultrasonography (EUS) or presence of paraaortic lymph node metastasis by CT and PET(short-axis diameter > 1 cm showing hot uptake in PET scan). Age 18-70 years old ECOG performance status 0-2 Adequate hepatic function(serum bilirubin <1.5mg/dl, AST (SGOT) and ALT (SGPT) < 2.5 x UNL, alkaline phosphatase < 5 x UNL) Adequate renal function(serum creatinine <1.5mg/dl) Adequate bone marrow function (WBC ≥4000 cell/㎕ with ANC ≥1500 cell/㎕, platelet count ≥100,000 cell/㎕) HER2 negative (HER2 immunohistochemistry 0 or 1+, immunohistochemistry 2+ but FISH negative) Informed consent Exclusion Criteria: Other histologic type than adenocarcinoma Metastasis in other sites than paraaortic lymph nodes, like in liver or peritoneum. Presence or history of other cancers History of prior chemotherapy, antiangiogenic agents, or radiation. Patients with definite ascites in abdomen CT scan Presence of not adequately controlled CNS metastasis Bowel obstruction Evidence of gastrointestinal bleeding Other serious illness or medical conditions including hypertension uncontrolled by medication. Pregnant or lactating women

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: neoadjuvant<br> | Drug: Docetaxel, Capecitabine, Cisplatin, Bevacizumab<br>* Bevacizumab 7.5mg/kg IV (D1) Docetaxel 60 mg/m2 IV (D1) Cisplatin 60 mg/m2 IV (D1) Xeloda 1,875 mg/m2/day/bid PO (D1-D14)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 resection rate | R0 resection means complete resection of tumor. | Up to 4 weeks after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival will be measured from the start of study treatment to documented death of any cause. | Up to 3 years | 
| Progression-free survival | Time to progression will be measured from the start of study treatment to documented tumor progression. | Up to 3 years | 
| Adverse Event | Treatment toxicities are evaluated according to the NCI common toxicity criteria version 3.0 | Up to 28 days after end of treatment | 
| Angiogenetic biomarkers | cluster of differentiation 31, microvessel density, platelet derived growth factor, vascular endothelial growth factor-A, vascular endothelial growth factor receptor-1, vascular endothelial growth factor receptor-2, Neuropilin 1 and phosphatidylinositol glycan anchor biosynthesis, class F | Baseline and 6 weeks after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced gastric cancer, Neoadjuvant, Bevacizumab