Capecitabine, Vorinostat, and Radiation Therapy in Treating Patients With Nonmetastatic Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00983268
Recruitment Status : Completed
First Posted : September 24, 2009
Last Update Posted : June 15, 2015
National Cancer Institute (NCI)
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Emily Chan, MD, PhD, Vanderbilt-Ingram Cancer Center

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Periampullary Adenocarcinoma Drug: capecitabine Drug: vorinostat Radiation: Radiotherapy Procedure: Surgery to remove tumor Phase 1

Detailed Description:



  • 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Trial of Chemoradiation With Capecitabine and Vorinostat in Pancreatic Cancer.
Study Start Date : October 2009
Actual Primary Completion Date : February 2013
Actual Study Completion Date : February 2013

Resource links provided by the National Library of Medicine

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 :
  1. Maximum tolerated dose of vorinostat when given in combination with capecitabine and radiotherapy [ Time Frame: Two weeks after completing radiotherapy ]

Secondary Outcome Measures :
  1. Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: Six weeks after completing chemo-radiation therpay ]
  2. Tumor response as assessed by RECIST criteria [ Time Frame: Six weeks after completing chemo-radiation therpay ]
  3. Biological effect [ Time Frame: Six weeks after completing chemo-radiation therapy ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00983268

United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
National Cancer Institute (NCI)
National Comprehensive Cancer Network
Principal Investigator: Emily Chan, M.D, Ph.D. Vanderbilt-Ingram Cancer Center

Additional Information:
Responsible Party: Emily Chan, MD, PhD, Assistant Professor of Medicine; Medical Oncologist, Vanderbilt-Ingram Cancer Center Identifier: NCT00983268     History of Changes
Other Study ID Numbers: VICC GI 0934
P30CA068485 ( U.S. NIH Grant/Contract )
IRB# 090791
First Posted: September 24, 2009    Key Record Dates
Last Update Posted: June 15, 2015
Last Verified: June 2015

Keywords provided by Emily Chan, MD, PhD, Vanderbilt-Ingram Cancer Center:
periampullary adenocarcinoma
stage I pancreatic cancer
stage II pancreatic cancer
stage III pancreatic cancer

Additional relevant MeSH terms:
Pancreatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors