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

Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00524069
• Other study ID #: I 68805
• Secondary ID: RPCI-I-68805
• Status: Withdrawn
• Phase: N/A
• First received: August 31, 2007
• Last updated: January 31, 2013
• Start date: January 2007

Study information

• Verified date: January 2013
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Biological:
• bevacizumab

Drug:
• capecitabine

• gemcitabine hydrochloride

Other:
• flow cytometry

• laboratory biomarker analysis

Procedure:
• adjuvant therapy

• computed tomography

• neoadjuvant therapy

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility and safety			Yes
Primary	Margin status after pancreatic resection			No
Secondary	Proportion of patients with positive resection margins, including microscopic (R1) or gross (R2) positive resection margins			No
Secondary	Median survival			No
Secondary	Time to recurrence			No
Secondary	Overall survival			No
Secondary	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			No
Secondary	Correlation of CEC number and VEGFR expression with margin positivity, survival, and recurrence			No
Secondary	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			No
Secondary	Toxicity			Yes