Bevacizumab, Oxaliplatin, and Docetaxel in Treating Patients With Locally Advanced Unresectable or Metastatic Stomach or Gastroesophageal Junction Cancer

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as oxaliplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with oxaliplatin and docetaxel may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bevacizumab together with oxaliplatin and docetaxel works in treating patients with locally advanced unresectable or metastatic stomach or gastroesophageal junction cancer.

Detailed Description
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OBJECTIVES: Primary Determine the time to progression in patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma treated with bevacizumab, oxaliplatin, and docetaxel. Secondary Determine the response rate in patients treated with this regimen. Determine the toxic effects of this regimen in these patients. Determine time to treatment failure and overall survival of patients treated with this regimen. Determine the changes in general and disease-specific quality of life, in terms of response to treatment, in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive bevacizumab IV over 30-90 minutes, oxaliplatin IV over 120 minutes, and docetaxel IV over 60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional courses beyond CR. After completion of study treatment, patients are followed periodically for up to 2 years. PROJECTED ACCRUAL: A total of 38 patients will be accrued for this study within 18-23 months.

Official Title
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Phase II Trial of Bevacizumab, Docetaxel, and Oxaliplatin in Gastric and Gastroesophageal Junction Cancer

Conditions
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Esophageal Cancer, Gastric Cancer

Intervention / Treatment
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* Biological: Bevacizumab
* Drug: Docetaxel
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed gastric or gastroesophageal junction adenocarcinoma Locally advanced unresectable or metastatic disease Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10mm by spiral CT scan Bone metastases, ascites, or pleural effusions are not considered measurable disease Evaluable disease must be present outside previously irradiated field No CNS or brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status SWOG 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10 mg/dL No evidence of bleeding diathesis or coagulopathy Hepatic AST and ALT ≤ 2.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN Bilirubin ≤ ULN INR < 1.5 Renal Creatinine < 2.0 mg/dL Urine protein:creatinine ratio < 1.0 Cardiovascular No history of deep venous thrombosis requiring anticoagulation No active angina No myocardial infarction within the past year No cerebrovascular accident within the past year No uncontrolled hypertension (systolic blood pressure [BP] > 170 mm Hg and/or diastolic BP > 100 mm Hg) despite medical management Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after completion of study treatment No peripheral neuropathy > grade 1 No history of allergy to any of the study drugs or drugs formulated with polysorbate 80 No known HIV infection No active peptic ulcer disease No serious non-healing wound, ulcer, or bone fracture No unresolved bacterial infection requiring antibiotics No other active malignancy within the past 3 years except for cancers that have been treated with a curative intent PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent immunotherapy Chemotherapy No prior chemotherapy for gastric cancer unless disease relapsed > 6 months after completion of non-taxane adjuvant chemotherapy No other concurrent chemotherapy Endocrine therapy Not specified Radiotherapy See Disease Characteristics At least 3 weeks since radiotherapy Surgery At least 4 weeks since prior surgery or open biopsy (except indwelling venous catheter placement) No concurrent surgery Other At least 4 weeks since prior and no concurrent participation in another experimental drug trial No concurrent full-dose anticoagulation No concurrent experimental drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Docetaxel, Oxaliplatin & Bevacizumab<br>Must be administered 1st before Docetaxel & Oxaliplatin.7.5 mg/kg, IV, day 1 of each cycle; During the first cycle, bevacizumab will be delivered over 90 + or - 15 minutes. If the 1st IV infusion is tolerated w/o infusion-associated adverse events, the 2nd infusion may be delivered over 60 + or - 10 minutes. If the 60 min infusion is well tolerated, all subsequent infusions may be delivered over 30 min + or - 10 mins. | Biological: Bevacizumab<br>* Must be administered 1st before Docetaxel & Oxaliplatin.7.5 mg/kg, IV, day 1 of each cycle; During the first cycle, bevacizumab will be delivered over 90 + or - 15 minutes. If the 1st IV infusion is tolerated w/o infusion-associated adverse events, the 2nd infusion may be delivered over 60 + or - 10 minutes. If the 60 min infusion is well tolerated, all subsequent infusions may be delivered over 30 min + or - 10 mins.<br>* Other names: Avastin;Drug: Docetaxel<br>* Must be administered 2nd after Bevacizumab and followed by Oxaliplatin.70 mg/m(2), IV over 60 minutes, day 1 of each cycle;<br>* Other names: Taxotere;Drug: Oxaliplatin<br>* Must be administered 3rd after Bevacizumab and Docetaxel. 75 mg/m(2), IV over 120 minutes, Day 1 of each cycle.<br>* Other names: Eloxatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | After every 2 cycles (1 cycle =21 days) From study registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate by RECIST Criteria | Percentage of Participants with response by RECIST criteria until progression | After every 2 cycles (1 cycle =21 days) | 
| Toxicity Profile | Toxicity profile of grade 3 and grade 4 events using the NCI-CTCAE Version 3.0 scale for toxicity grading. | At 21 days following completion of study treatment | 
| Time to Treatment Failure | Time to treatment failure using the Kaplan-Meier method | Every 21 days From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 
| Overall Survival | Overall survival using the Kaplan-Meier method | Patients will be followed for survival every three months after they are off study or until their disease progresses, for up to two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent esophageal cancer, recurrent gastric cancer, stage III gastric cancer, stage IV gastric cancer, stage III esophageal cancer, stage IV esophageal cancer, adenocarcinoma of the stomach