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

Vanderbilt University Medical Center

Status and phase

Completed

Phase 1

Conditions

Periampullary Adenocarcinoma

Pancreatic Cancer

Treatments

Procedure: Surgery to remove tumor

Drug: vorinostat

Radiation: Radiotherapy

Drug: capecitabine

Study type

Interventional

Funder types

Other

NETWORK

NIH

Identifiers

NCT00983268

VICC GI 0934

NCCN-M02

P30CA068485 (U.S. NIH Grant/Contract)

VU-VICC-GI-0934

IRB# 090791

Details and patient eligibility

About

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.

Full 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.

Enrollment

21 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.