Gemcitabine, Capecitabine, And Bevacizumab In Treating Patients With Pancreatic Cancer That Can Be Removed By Surgery

Study Overview

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

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.

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.

Pancreatic Cancer

BIOLOGICAL: bevacizumab
DRUG: capecitabine
DRUG: gemcitabine hydrochloride
OTHER: flow cytometry
OTHER: laboratory biomarker analysis
PROCEDURE: adjuvant therapy
PROCEDURE: computed tomography
PROCEDURE: neoadjuvant therapy

I 68805
RPCI-I-68805

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2007-08-31	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2013-01-31
First Submitted that Met QC Criteria 2007-08-31	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2013-02-01
First Posted (ESTIMATED) 2007-09-03	Results First Posted N/A	Last Verified 2013-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
N/A

Interventional Model:
N/A

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment

Primary Outcome Measures	Measure Description	Time Frame
Feasibility and safety
Margin status after pancreatic resection

Secondary Outcome Measures	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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Renuka Iyer, MD, Roswell Park Cancer Institute

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Resources

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Clinical Trial Record