Capecitabine, Vorinostat, And Radiation Therapy In Treating Patients With Nonmetastatic Pancreatic Cancer

Study Overview

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.

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.

Pancreatic Cancer
Periampullary Adenocarcinoma

DRUG: capecitabine
DRUG: vorinostat
RADIATION: Radiotherapy
PROCEDURE: Surgery to remove tumor

VICC GI 0934
P30CA068485 (U.S. NIH Grant/Contract)
VU-VICC-GI-0934
IRB# 090791
NCCN-M02

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2009-09-23	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2015-06-11
First Submitted that Met QC Criteria 2009-09-23	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2015-06-15
First Posted (ESTIMATED) 2009-09-24	Results First Posted N/A	Last Verified 2015-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment Arm	DRUG: capecitabine 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: * Vorinostat,at 100 mg * Vorinostat,at 200 mg * Vorinostat, at 300 mg * Vorinostat, at 400 mg RADIATION: Radiotherapy 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.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment Arm

DRUG: capecitabine

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: * Vorinostat,at 100 mg * Vorinostat,at 200 mg * Vorinostat, at 300 mg * Vorinostat, at 400 mg

RADIATION: Radiotherapy

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.

Primary Outcome Measures	Measure Description	Time Frame
Maximum tolerated dose of vorinostat when given in combination with capecitabine and radiotherapy		Two weeks after completing radiotherapy

Secondary Outcome Measures	Measure Description	Time Frame
Toxicity as assessed by NCI CTCAE v3.0		Six weeks after completing chemo-radiation therpay
Tumor response as assessed by RECIST criteria		Six weeks after completing chemo-radiation therpay
Biological effect		Six weeks after completing chemo-radiation therapy

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)
National Comprehensive Cancer Network

Investigators

PRINCIPAL_INVESTIGATOR: Emily Chan, M.D, Ph.D., Vanderbilt-Ingram Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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