Gemcitabine and Bevacizumab in Treating Patients With Pancreatic Cancer That Has Been Completely Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine, 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 and 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 and bevacizumab after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase I/II trial is studying the side effects of gemcitabine and bevacizumab and to see how well they work in treating patients with pancreatic cancer that has been completely removed by surgery.

Detailed Description
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OBJECTIVES: Primary Determine the safety of adjuvant, fixed-dose rate gemcitabine hydrochloride and bevacizumab in patients with completely resected pancreatic cancer. Determine the 1-year disease-free survival rate in patients treated with this regimen. Secondary Determine the 1- and 2-year overall survival rates in these patients. Determine the median disease-free survival rate in these patients. Determine the median overall survival rate in these patients. OUTLINE: This is an open-label, non-randomized study. Patients receive gemcitabine hydrochloride IV over 100 minutes followed by bevacizumab* IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease recurrence or unacceptable toxicity. NOTE: *The first dose of bevacizumab is not administered until after 6 weeks have passed since surgery. After completion of study therapy, patients are followed periodically for 18 months. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Official Title
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A Phase I/II Study of Fixed-Dose Rate Gemcitabine and Bevacizumab for Postoperative Adjuvant Treatment of Patients With Resected Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Biological: bevacizumab
* Drug: gemcitabine hydrochloride
* Procedure: adjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the pancreas Completely resected disease Underwent 1 of the following procedures 3-8 weeks ago: Standard pancreaticoduodenectomy (for tumors of the pancreatic head) Distal pancreatectomy (for tumors of the pancreatic tail) No grossly positive surgical margins Positive microscopic margins allowed Nonmeasurable disease No known CNS disease PATIENT CHARACTERISTICS: ECOG performance status 0-1 Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after completion of study therapy CA 19-9 ≤ 2.5 times upper limit of normal (ULN) Absolute neutrophil count ≥ 1,500/mm³ Hemoglobin ≥ 9 g/dL (transfusion or epoetin alfa allowed) Platelet count ≥ 100,000/mm³ INR ≤ 1.5 (except in patients receiving full-dose warfarin) Bilirubin ≤ 2.0 mg/dL AST and ALT ≤ 2.5 times ULN Creatinine ≤ 2.0 mg/dL No clinically significant impairment of renal function No postoperative complications, including any of the following: Wound dehiscence or infection Intra-abdominal abscess Pancreatic or biliary leak or fistula Grade 3 or 4 delayed hemorrhage (occurring > 5 days postoperatively) Bowel perforation No abdominal fistula, gastrointestinal perforation, or intra-abdominal abcess within the past 6 months No history of major psychiatric disorder or other chronic medical illness that, in the opinion of the treating physician, contraindicates use of the study drugs or renders the patient at high risk of treatment-related complications No other cancer within the past 5 years except basal cell or squamous cell skin cancer No history of serious systemic disease, including any of the following: Myocardial infarction or unstable angina within the past 12 months New York Heart Association class II-IV congestive heart failure Unstable symptomatic arrhythmia requiring medication Chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) allowed No history of stroke or transient ischemic attack No symptomatic peripheral vascular disease No significant vascular disease (e.g., aortic aneurysm, aortic dissection) No inadequately controlled hypertension (i.e., blood pressure > 150/100 mm Hg on antihypertensive medication) No prior hypertensive crisis or hypertensive encephalopathy No proteinuria (defined as urine protein:creatinine ratio ≥ 1.0 OR proteinuria ≥ 2+ by dipstick urinalysis OR protein > 1 g by 24-hour urine collection) No serious, nonhealing wound or ulcer No evidence of bleeding diathesis or coagulopathy No significant traumatic injury within the past 28 days PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior chemotherapy or radiotherapy for pancreatic cancer No prior systemic or investigational therapy for pancreatic cancer No major surgical procedure (except for resection of pancreatic cancer) or open biopsy within the past 28 days No fine-needle aspiration or core biopsy within the past 7 days No anticipated need for a major surgical procedure during study treatment No concurrent newly prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) Concurrent chronic-dose NSAIDs for analgesia are allowed

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
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: bevacizumab|nan|
|Drug: gemcitabine hydrochloride|nan|
|Procedure: adjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of gemcitabine when administered with bevacizumab as assessed by NCI CTCAE v3.0 |  |  | 
| Disease-free survival rate at 1 year |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival rate at 1 and 2 years |  |  | 
| Median disease-free survival rate at 1 and 2 years |  |  | 
| Median overall survival rate at 1 and 2 years |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III pancreatic cancer, stage I pancreatic cancer, adenocarcinoma of the pancreas, stage II pancreatic cancer