- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00983268
Capecitabine, Vorinostat, and Radiation Therapy in Treating Patients With Nonmetastatic Pancreatic Cancer
Phase I Trial of Chemoradiation With Capecitabine and Vorinostat in 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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of vorinostat when given in combination with capecitabine and high-dose hypofractionated radiotherapy in patients with nonmetastatic pancreatic cancer.
Secondary
- Determine the safety and side effect profile of this regimen in these patients.
- Determine the response rate in patients treated with this regimen.
Correlative
- 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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Tennessee
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Nashville, Tennessee, United States, 37232-6838
- Vanderbilt-Ingram Cancer Center
-
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patient must have histologically confirmed pancreatic or periampullary cancer.
- Patient must be > 18 years of age.
- Patient may be resectable, borderline resectable, or unresectable but locally advanced as determined by radiographic examination and consultation with a surgical oncologist.
- Patient must have Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.
- Female patients of childbearing potential must be willing to use birth control. The 2 birth control methods can be either 2 barrier methods or a barrier method plus a hormonal method to prevent pregnancy, used throughout the study starting with visit 1. The following are considered adequate barrier methods of contraception: diaphragm, condom (by the partner) or sponge. Other methods of contraception such as copper intrauterine device or spermicide may be used. Appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular agents).Female patient of childbearing potential has a negative serum pregnancy test β-hCG within 7 days prior to receiving the first dose of vorinostat.
- Male patients agree to use an adequate method of contraception for the duration of the study.
- Patient has a life expectancy of at least 12 weeks
- Patient must have adequate organ function as indicated by the following laboratory values:
- Absolute neutrophil count (ANC) ≥1,500 /mcL
- Platelets ≥100,000 / mcL Hemoglobin ≥ 9 g/dL
- Coagulation
- Prothrombin Time or INR ≤1.5x upper limit of normal (ULN) unless receiving therapeutic anticoagulation
- Partial thromboplastin time (PTT) ≤1.2 times the ULN unless the patient is receiving therapeutic anticoagulation.
- K levels - Normal limits
- Mg levels - Normal limits
- Calculated creatinine *clearance ≥20 mL/min
- Serum total bilirubin ≤ 1.5 X ULN
- AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN
Alkaline Phosphatase ≤ 2.5 X ULN
* Creatinine clearance should be calculated per institutional standard.
- Patient must be capable of understanding and complying with the study protocol and able to give informed consent.
- Measurable disease is not an eligibility requirement.
Exclusion Criteria:
- Prior chemotherapy for pancreatic or periampullary cancer.
- Prior radiation to any area within the planned radiation field. All patients with history of prior radiation to any area must be approved by PI.
- Evidence of distant metastases on imaging.
- History of hypersensitivity to fluoropyrimidines or HDACs.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment Arm
|
1000 mg taken by mouth on the days of radiation only.
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.
Patients will be assessed for resectability within six weeks of the end of chemoradiation, if resectable, surgery will be performed.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Maximum tolerated dose of vorinostat when given in combination with capecitabine and radiotherapy
Time Frame: Two weeks after completing radiotherapy
|
Two weeks after completing radiotherapy
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Toxicity as assessed by NCI CTCAE v3.0
Time Frame: Six weeks after completing chemo-radiation therpay
|
Six weeks after completing chemo-radiation therpay
|
Tumor response as assessed by RECIST criteria
Time Frame: Six weeks after completing chemo-radiation therpay
|
Six weeks after completing chemo-radiation therpay
|
Biological effect
Time Frame: Six weeks after completing chemo-radiation therapy
|
Six weeks after completing chemo-radiation therapy
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Emily Chan, M.D, Ph.D., Vanderbilt-Ingram Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Endocrine System Diseases
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Pancreatic Diseases
- Adenocarcinoma
- Pancreatic Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Histone Deacetylase Inhibitors
- Capecitabine
- Vorinostat
Other Study ID Numbers
- VICC GI 0934
- P30CA068485 (U.S. NIH Grant/Contract)
- VU-VICC-GI-0934
- IRB# 090791
- NCCN-M02
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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