Capecitabine, Vorinostat, and Radiation Therapy in Treating Patients With Nonmetastatic Pancreatic Cancer - Full Text View

Sponsor:	Vanderbilt-Ingram Cancer Center
Collaborators:	National Cancer Institute (NCI) National Comprehensive Cancer Network
Information provided by (Responsible Party):	Emily Chan, MD, PhD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:	NCT00983268

Purpose

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	Intervention	Phase
Pancreatic Cancer Periampullary Adenocarcinoma	Drug: capecitabine Drug: vorinostat Radiation: Radiotherapy Procedure: Surgery to remove tumor	Phase 1

Study Type:	Interventional
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.

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Vorinostat Capecitabine

U.S. FDA Resources

Further study details as provided by Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	15
Study Start Date:	October 2009
Estimated Study Completion Date:	May 2015
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Arms

Assigned Interventions

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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00983268

Contacts

Contact: VICC Clinical Trials Information Program

1-800-811-8480

Locations

United States, Tennessee
Vanderbilt-Ingram Cancer Center	Recruiting
Nashville, Tennessee, United States, 37232-6838
Contact: Clinical Trials Office - Vanderbilt-Ingram Cancer Center 800-811-8480

Sponsors and Collaborators

Vanderbilt-Ingram Cancer Center

National Cancer Institute (NCI)

National Comprehensive Cancer Network

Investigators

Principal Investigator:

Emily Chan, M.D, Ph.D.

Vanderbilt-Ingram Cancer Center

More Information

Additional Information:

Vanderbilt-Ingram Cancer Center, Find a Clinical Trial This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Emily Chan, MD, PhD, Assistant Professor of Medicine; Medical Oncologist, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:	NCT00983268 History of Changes
Other Study ID Numbers:	VICC GI 0934, P30CA068485, VU-VICC-GI-0934, IRB# 090791, NCCN-M02
Study First Received:	September 23, 2009
Last Updated:	January 4, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Vanderbilt-Ingram Cancer Center:

periampullary adenocarcinoma
stage I pancreatic cancer
stage II pancreatic cancer
stage III pancreatic cancer

Additional relevant MeSH terms:

Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Capecitabine

Fluorouracil
Vorinostat
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Histone Deacetylase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 24, 2012