Gemcitabine Hydrochloride With or Without Bevacizumab in Treating Patients Who Are Undergoing Surgery for Pancreatic Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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 an help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of pancreatic cancer by blocking blood flow to the tumor. Giving gemcitabine hydrochloride together with bevacizumab after surgery may kill any remaining tumor cells. PURPOSE: This phase II trial is studying gemcitabine hydrochloride and bevacizumab to see how well they work compared to gemcitabine hydrochloride alone in treating patients who are undergoing surgery for pancreatic cancer.

Detailed Description
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OBJECTIVES: Primary Compare the disease-free interval in patients with adenocarcinoma of the pancreas treated with surgical resection followed by adjuvant gemcitabine hydrochloride with vs without bevacizumab. Secondary Compare overall survival in patients treated with these regimens. Evaluate tumor gene expression profiles and levels of tumor angiogenesis markers to establish prognostic indicators for response in patients treated with these regimens. OUTLINE: This is a randomized, controlled study. All patients undergo surgical resection for the pancreatic tumor. Within 4-8 weeks after surgery, patients are stratified according to projected 2-year survival (≤ 5% vs > 5% and ≤ 33% vs > 33%). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive gemcitabine hydrochloride IV over 100 minutes on days 1, 8, and 15, and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses. Patients then receive bevacizumab IV alone every 2 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive gemcitabine hydrochloride IV over 100 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 130 patients will be accrued for this study.

Official Title
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Phase II Randomized Study of Surgical Resection and Adjuvant Gemcitabine Hydrochloride With Versus Without Bevacizumab in Patients With Adenocarcinoma of the Pancreas

Conditions
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Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage I Pancreatic Cancer, Stage II Pancreatic Cancer, Stage III Pancreatic Cancer

Intervention / Treatment
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* Drug: bevacizumab
* Drug: gemcitabine hydrochloride
* Procedure: adjuvant therapy
* Procedure: anti-cytokine therapy
* Procedure: antiangiogenesis therapy
* Procedure: antibody therapy
* Procedure: biological therapy
* Procedure: chemotherapy
* Procedure: conventional surgery
* Procedure: growth factor antagonist therapy
* Procedure: monoclonal antibody therapy
* Procedure: surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the pancreas No evidence of distant metastasis on laparoscopy No superior mesenteric artery or thrombosed superior mesenteric vein involvement Superior mesenteric vein or portal vein involvement allowed Evidence of a pancreatic mass by radiographic or endoscopic examination PATIENT CHARACTERISTICS: Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic WBC ≥ 2,500/mm^3 Absolute neutrophil count ≥ 1,250/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Hepatitis B surface antigen negative Hepatitis C virus negative No history of hepatic cirrhosis Renal Creatinine ≤ 2.0 mg/dL Proteinuria negative or trace by urinalysis OR Protein < 1 g on 24 hr urine collection No active gross hematuria Cardiovascular No severe congestive heart failure No active ischemic heart disease No ischemic changes on a cardiac thallium stress test No uncontrolled hypertension (i.e., blood pressure ≤ 150/100 mm Hg despite antihypertensive therapy) No active coagulation disorder Pulmonary No active gross hemoptysis Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during the adjuvant therapy part of trial HIV negative No active infection No wound healing problem from recent invasive procedure No significant history of medical illness that would preclude patient from undergoing an operative procedure No other malignancy requiring systemic therapy PRIOR CONCURRENT THERAPY: Biologic therapy Recovered from prior immunotherapy for pancreatic cancer No prior bevacizumab Chemotherapy Recovered from prior chemotherapy for pancreatic cancer No prior gemcitabine hydrochloride Endocrine therapy Recovered from prior hormonal therapy for pancreatic cancer Radiotherapy Recovered from prior radiotherapy for pancreatic cancer No prior radiotherapy to the pancreas Surgery No prior definitive resection of the primary pancreatic tumor Prior surgery, other than resection of the primary tumor, allowed Other More than 3 weeks since prior systemic therapy for this cancer No concurrent therapeutic anticoagulation causing elevated PT or PTT

Ages Eligible for Study
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Minimum Age: 18 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: bevacizumab|nan|
|Drug: gemcitabine hydrochloride|nan|
|Procedure: adjuvant therapy|nan|
|Procedure: anti-cytokine therapy|nan|
|Procedure: antiangiogenesis therapy|nan|
|Procedure: antibody therapy|nan|
|Procedure: biological therapy|nan|
|Procedure: chemotherapy|nan|
|Procedure: conventional surgery|nan|
|Procedure: growth factor antagonist therapy|nan|
|Procedure: monoclonal antibody therapy|nan|
|Procedure: surgery|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |