A Phase II Study of Gemcitabine, Oxaliplatin and Bevacizumab Followed by 5-Fluorouracil, Oxaliplatin, Bevacizumab and Radiotherapy in Patients With Locally Advanced Pancreatic Cancer
- 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
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.
Masking: Open Label, Primary Purpose: Treatment
Response rate after 6 and 12 weeks of pre-radiation chemotherapy and bevacizumab and after 5-6 weeks of concurrent chemoradiotherapy and bevacizumab
Amy Kramer, RN, MPA
Abramson Cancer Center of the University of Pennsylvania
|Abramson Cancer Center of the University of Pennsylvania||Philadelphia, Pennsylvania 19104-4283|