Gemcitabine, Capecitabine, and Bevacizumab in Treating Patients With Pancreatic Cancer That Can Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine and capecitabine, 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 tumor cells by blocking blood flow to the tumor. Giving gemcitabine and capecitabine together with bevacizumab may kill more tumor cells. PURPOSE: This clinical trial is studying the side effects and how well giving gemcitabine and capecitabine together with bevacizumab works in treating patients with pancreatic cancer that can be removed by surgery.

Detailed Description
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OBJECTIVES: Primary To determine the feasibility and safety of bevacizumab-based neoadjuvant and adjuvant therapy in patients with resectable pancreatic adenocarcinoma. To determine the proportion of patients with margin-positive resections after pancreatic resection. Secondary To estimate overall survival of patients treated with this regimen. To assess the time to recurrence in patients treated with this regimen. To measure the change in the number of circulating endothelial precursor cells (CEC) and VEGF expression on CEC at baseline and after the start of neoadjuvant therapy and examine their relationship with response, time to recurrence, and survival. To assess the utility of dynamic contrast-enhanced spiral CT scan as surrogate endpoints for antiangiogenic therapy. OUTLINE: This is a multicenter study. Neoadjuvant therapy: Patients receive gemcitabine IV over 30 minutes on days 1 and 8; oral capecitabine twice daily on days 1-14; and bevacizumab* IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. NOTE: *Patients receive bevacizumab during courses 1 and 2 only. Surgical resection: Within 6-8 weeks after the last dose of bevacizumab, patients undergo surgical resection of the pancreatic tumor. Adjuvant therapy: Beginning 6-10 weeks after surgery, patients receive up to 6 additional courses of gemcitabine, capecitabine, and bevacizumab as in neoadjuvant therapy. Patients undergo blood sample collection at baseline and periodically during study for biomarker correlative studies. Samples are analyzed by flow cytometry to measure levels of circulating endothelial precursor cells and VEGF markers of angiogenesis. Patients also undergo dynamic contrast-enhanced (DCE) spiral CT scan of the abdomen. DCE-CT imaging studies are performed at baseline and after completion of neoadjuvant therapy (1-2 weeks prior to surgical resection) to assess changes in tumor blood flow, blood volume, and tumor vasculature. After completion of study therapy, patients are followed periodically for at least 5 years.

Official Title
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A Pilot Study of Bevacizumab Based Peri-Operative Therapy for Operable Pancreatic Adenocarcinoma

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Biological: bevacizumab
* Drug: capecitabine
* Drug: gemcitabine hydrochloride
* Other: flow cytometry
* Other: laboratory biomarker analysis
* Procedure: adjuvant therapy
* Procedure: computed tomography
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed pancreatic adenocarcinoma Resectable disease (i.e., stage I or II disease) No unresectable (i.e., locally advanced) disease No tumor invasion into the stomach or duodenum No CNS, brain, or systemic metastases PATIENT CHARACTERISTICS: ECOG performance status 0-1 WBC > 3,000/μL ANC > 1,500/μL Platelet count > 100,000/μL Total bilirubin < 2 mg/dL AST or ALT < 2.5 times upper limit of normal (ULN) Creatinine < 1.5 mg/dL Creatinine clearance ≥ 50 mL/min Urine protein:creatinine ratio < 1.0 Hemoglobin ≥ 9 g/dL (transfusion, epoetin alfa, or darbepoetin allowed) INR < 1.5 times ULN (except in patients receiving full-dose warfarin) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No uncontrolled hypertension No unstable angina No New York Heart Association class II-IV congestive heart failure No myocardial infarction or stroke within the past 6 months No clinically significant peripheral vascular disease No evidence of bleeding diathesis or coagulopathy No significant traumatic injury within the past 28 days No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months No esophageal or gastric varices No serious nonhealing wound, ulcer, or bone fracture PRIOR CONCURRENT THERAPY: No prior therapy for pancreatic cancer More than 4 weeks since prior and no concurrent participation in another experimental drug study More than 28 days since prior major surgical procedure or open biopsy More than 7 days since prior minor surgical procedure (e.g., fine-needle aspiration or core biopsy)

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: bevacizumab|nan|
|Drug: capecitabine|nan|
|Drug: gemcitabine hydrochloride|nan|
|Other: flow cytometry|nan|
|Other: laboratory biomarker analysis|nan|
|Procedure: adjuvant therapy|nan|
|Procedure: computed tomography|nan|
|Procedure: neoadjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility and safety |  |  | 
| Margin status after pancreatic resection |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with positive resection margins, including microscopic (R1) or gross (R2) positive resection margins |  |  | 
| Median survival |  |  | 
| Time to recurrence |  |  | 
| Overall survival |  |  | 
| Number of circulating endothelial precursor cells (CEC) and their VEGFR expression as measured by flow cytometry at baseline and after the start of neoadjuvant therapy |  |  | 
| Correlation of CEC number and VEGFR expression with margin positivity, survival, and recurrence |  |  | 
| Changes in blood volume, blood flow, mean transit time, and color flow maps of the tumor as measured by dynamic contrast-enhanced spiral CT scan at baseline and after completion of neoadjuvant therapy |  |  | 
| Toxicity |  |  | 

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