Phase I Trial of Chemoradiation With Capecitabine and Vorinostat in Pancreatic Cancer.
- Determine the maximum tolerated dose of vorinostat when given in combination with
capecitabine and high-dose hypofractionated radiotherapy in patients with nonmetastatic
- Determine the safety and side effect profile of this regimen in these patients.
- Determine the response rate in patients treated with this regimen.
- Compare pre- and post-treatment whole-cell HDAC-activity levels in peripheral blood
mononuclear cell samples.
- Assess chromatin structure and DNA damage in surgical tumor tissue samples.
- Assess proliferation and apoptosis by in vivo imaging.
OUTLINE: This is a dose-escalation study of vorinostat.
Patients receive oral capecitabine twice daily and undergo high-dose hypofractionated
radiotherapy once daily on days 1-5 and 8-12. Patients also receive oral vorinostat once
daily on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or
Patients are evaluated for surgery within 6 weeks after completion of chemoradiotherapy.
Patients with resectable disease proceed to surgery. Patients with unresectable disease may
receive oral vorinostat once daily and oral capecitabine twice daily on days 1-14. Courses
repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for correlative laboratory studies. Patients also
undergo diffusion-weighted MRI for analysis of in vivo tumor cellularity.
After completion of study therapy, patients are followed up periodically for 5 years.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of vorinostat when given in combination with capecitabine and radiotherapy
Two weeks after completing radiotherapy
Emily Chan, M.D, Ph.D.
Vanderbilt-Ingram Cancer Center
United States: Food and Drug Administration
VICC GI 0934
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|