Bevacizumab, Combination Chemotherapy, and Radiation Therapy in Treating Patients Undergoing Surgery For Locally Advanced Pancreatic Cancer
RATIONALE: 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. Drugs used in chemotherapy, such as gemcitabine, oxaliplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bevacizumab together with combination chemotherapy and radiation therapy may kill more tumor cells.
PURPOSE: The phase II trial is studying the side effects and how well giving bevacizumab together with gemcitabine, oxaliplatin, fluorouracil, and radiation therapy works in treating patients undergoing surgery for locally advanced pancreatic cancer.
|Pancreatic Cancer||Biological: bevacizumab Drug: fluorouracil Drug: gemcitabine hydrochloride Drug: oxaliplatin Other: immunohistochemistry staining method Other: laboratory biomarker analysis Procedure: conventional surgery Procedure: endoscopic biopsy Procedure: laparoscopy Radiation: radiation therapy||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Gemcitabine, Oxaliplatin and Bevacizumab Followed by 5-Fluorouracil, Oxaliplatin, Bevacizumab and Radiotherapy in Patients With Locally Advanced Pancreatic Cancer|
- Response rate after 6 and 12 weeks of pre-radiation chemotherapy and bevacizumab and after 5-6 weeks of concurrent chemoradiotherapy and bevacizumab
- Time to progression after 6 and 12 weeks of pre-radiation chemotherapy and bevacizumab and after 5-6 weeks of concurrent chemoradiotherapy and bevacizumab
- Progression-free survival
- Overall survival
- Percentage of potentially resectable patients who are able to proceed to successful resection
|Study Start Date:||March 2007|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
- To describe the toxicity of bevacizumab with gemcitabine and oxaliplatin, when therapy is given before chemoradiotherapy, in patients with locally advanced pancreatic cancer.
- To describe the toxicity of bevacizumab with oxaliplatin, fluorouracil, and concomitant radiotherapy in these patients.
- To define progression-free survival, time to progression, and overall survival of patients treated with this regimen.
- To determine the percentage of potentially resectable patients who are ultimately able to proceed to successful resection.
- To determine the relationship between markers of apoptosis in tumor cells (including MIF, CREB, HIF-1-alpha expression/polymorphism, and others) and response to therapy.
- To define response rates in patients treated with this regimen.
- Neoadjuvant therapy: Patients receive gemcitabine IV over 100 minutes and bevacizumab IV over 30-90 minutes on day 1 and oxaliplatin IV over 2 hours on day 2. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Between 4-6 weeks after completion of initial therapy, patients undergo radiotherapy once daily, 5 days a week, for 5-6 weeks. Beginning within 48 hours after initiation of radiotherapy, patients receive fluorouracil IV continuously through completion of radiotherapy. Patients also receive concurrent oxaliplatin IV over 2 hours on days 1, 15 and 29 and bevacizumab IV on days 1 and 15.
- Surgery: Four to six weeks after completion of neoadjuvant therapy, patients undergo resection of the tumor. Patients with no evidence of disease progression and who undergo successful surgical intervention (i.e., R0 resection) proceed to adjuvant chemotherapy within the next 6-10 weeks.
- Adjuvant therapy: Patients receive gemcitabine and bevacizumab for 4 courses as in neoadjuvant therapy.
Patients undergo collection of tumor tissue samples at the time of diagnosis, prior to treatment by endoscopic ultrasound or laparoscopy, or during surgical resection following neoadjuvant therapy. Paraffin-embedded tumor tissue specimens obtained at baseline are analyzed by immunohistochemistry to assess tumor vascularity and angiogenic activity. Tumor vascularity is assessed via immunostaining of tumor specimens with the pan-endothelial cell marker, anti-CD34, for evaluation of tumor blood vessels. Angiogenic activity is assessed by analyzing pERK1/2, Ki67, and the pericyte coverage index in tumor specimens. Patients also undergo blood collection to determine plasma levels of VEGF at 4 weeks prior to initial chemotherapy and bevacizumab, at up to 48 hours prior to chemoradiotherapy and bevacizumab, and at up to 48 hours prior to adjuvant chemotherapy and bevacizumab.
After completion of study therapy, patients are followed every 2 months for the first year, and then every 3 months thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00602602
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104-4283|
|Principal Investigator:||Peter O'Dwyer, MD||Abramson Cancer Center of the University of Pennsylvania|