Bevacizumab and Gemcitabine in Treating Patients With Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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This phase II trial is to see if combining gemcitabine with bevacizumab works in treating patients who have advanced pancreatic cancer. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Combining chemotherapy with a monoclonal antibody may kill more tumor cells

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the objective response rate of patients with advanced pancreatic cancer who are treated with gemcitabine plus bevacizumab. II. To determine the toxicity experienced by patients with advanced pancreatic cancer who are treated with gemcitabine plus bevacizumab. III. To determine median and overall survival of patients with advanced pancreatic cancer who are treated with gemcitabine plus bevacizumab. SECONDARY OBJECTIVES: I. To measure plasma VEGF and serum VCAM-1 levels before, during, and after therapy as a predictor of outcome. II. To collect and store serum samples for possible future assessment of other antiangiogenic inhibition markers. OUTLINE: This is a multicenter study. Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Official Title
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A Phase II Trial Of Bevacizumab (NSC#704865) Plus Gemcitabine In Patients With Advanced Pancreatic Cancer

Conditions
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Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Biological: bevacizumab
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed pancreatic adenocarcinoma Not amenable to curative treatment with surgery or radiotherapy Locally advanced disease must extend outside the boundaries of a standard radiation port At least 1 unidimensionally measurable lesion At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan Pleural effusions and ascites not considered measurable lesions No obvious tumor involvement of major vessels on CT scan No known brain metastases Performance status - ECOG 0-2 More than 3 months WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 No prior bleeding diathesis Bilirubin normal AST/ALT no greater than 2.5 times upper limit of normal PT INR no greater than 1.5 Creatinine no greater than 1.5 mg/dL Creatinine clearance at least 60 mL/min Urine protein less than 500 mg/24 hours if at least 1+ proteinuria No significant renal impairment No prior cardiovascular accident No prior deep vein thrombosis No myocardial ischemia or infarction within the past 6 months No uncompensated coronary artery disease within the past 6 months No uncontrolled hypertension No symptomatic congestive heart failure No cardiac arrhythmia No clinically significant peripheral artery disease No arterial thromboembolic event within the past 6 months, including any of the following: Transient ischemic attack Cerebrovascular accident Unstable angina Myocardial infarction No prior pulmonary embolism No concurrent uncontrolled illness No ongoing or active infection No other concurrent active malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix No psychiatric illness or social situation that would preclude study entry No prior allergic reaction attributed to compounds of similar chemical or biologic composition to bevacizumab or other agents (Chinese hamster ovary cell products or other recombinant human antibodies) used in this study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No prior bevacizumab No prior cytotoxic chemotherapy for metastatic disease No prior gemcitabine At least 4 weeks since prior adjuvant chemotherapy and recovered At least 4 weeks since prior radiotherapy and recovered No prior radiotherapy to sole site of measurable disease At least 6 weeks since prior major surgery At least 30 days since prior investigational agents At least 1 month since prior and no concurrent thrombolytic agents or full-dose anticoagulants (except to maintain patency of pre-existing permanent indwelling IV catheters) No concurrent chronic daily aspirin (more than 325 mg/day) or nonsteroidal anti-inflammatory drugs known to inhibit platelet function No other concurrent investigational agents No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent anticancer therapy

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (gemcitabine hydrochloride, bevacizumab)<br>Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: gemcitabine hydrochloride<br>* Given IV<br>* Other names: Gemzar;Biological: bevacizumab<br>* Given IV<br>* Other names: rhuMAb VEGF;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (complete or partial responses) |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Calculated using the Kaplan-Meier method, and the median progression-free survival times and the associated 95% confidence intervals derived. | Up to 2 years | 
| Overall survival | Calculated using the Kaplan-Meier method, and the median overall survival times and the associated 95% confidence intervals derived. | Up to 2 years |