Capecitabine, Vorinostat, and Radiation Therapy in Treating Patients With Nonmetastatic Pancreatic Cancer
RATIONALE: Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells. Giving capecitabine and vorinostat together with radiation therapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat when given together with capecitabine and radiation therapy in treating patients with nonmetastatic pancreatic cancer.
Procedure: Surgery to remove tumor
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial of Chemoradiation With Capecitabine and Vorinostat in Pancreatic Cancer.|
- Maximum tolerated dose of vorinostat when given in combination with capecitabine and radiotherapy [ Time Frame: Two weeks after completing radiotherapy ] [ Designated as safety issue: Yes ]
- Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: Six weeks after completing chemo-radiation therpay ] [ Designated as safety issue: Yes ]
- Tumor response as assessed by RECIST criteria [ Time Frame: Six weeks after completing chemo-radiation therpay ] [ Designated as safety issue: No ]
- Biological effect [ Time Frame: Six weeks after completing chemo-radiation therapy ] [ Designated as safety issue: No ]
|Study Start Date:||October 2009|
|Estimated Study Completion Date:||March 2018|
|Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
|Experimental: Treatment Arm||
1000 mg taken by mouth on the days of radiation only.Drug: vorinostat
Vorinostat will be given by mouth on the day of radiation and then Monday-Friday for two weeks after radiation in these 4 possible doses:
High-dose hypofractionated radiotherapy consisting of 3000 cGy in 10 fractions, Monday-Friday for 2 weeks.Procedure: Surgery to remove tumor
Patients will be assessed for resectability within six weeks of the end of chemoradiation, if resectable, surgery will be performed.
- Determine the maximum tolerated dose of vorinostat when given in combination with capecitabine and high-dose hypofractionated radiotherapy in patients with nonmetastatic pancreatic cancer.
- 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 unacceptable toxicity.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00983268
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232-6838|
|Principal Investigator:||Emily Chan, M.D, Ph.D.||Vanderbilt-Ingram Cancer Center|