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

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.

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