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.
Drug: gemcitabine hydrochloride
Other: flow cytometry
Other: laboratory biomarker analysis
Procedure: adjuvant therapy
Procedure: computed tomography
Procedure: neoadjuvant therapy
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Bevacizumab Based Peri-Operative Therapy for Operable Pancreatic Adenocarcinoma|
- Feasibility and safety [ Designated as safety issue: Yes ]
- Margin status after pancreatic resection [ Designated as safety issue: No ]
- Proportion of patients with positive resection margins, including microscopic (R1) or gross (R2) positive resection margins [ Designated as safety issue: No ]
- Median survival [ Designated as safety issue: No ]
- Time to recurrence [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- 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 [ Designated as safety issue: No ]
- Correlation of CEC number and VEGFR expression with margin positivity, survival, and recurrence [ Designated as safety issue: No ]
- 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 [ Designated as safety issue: No ]
- Toxicity [ Designated as safety issue: Yes ]
|Study Start Date:||January 2007|
|Primary Completion Date:||November 2007 (Final data collection date for primary outcome measure)|
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00524069
|Principal Investigator:||Renuka Iyer, MD||Roswell Park Cancer Institute|