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

Pancreatic Cancer Clinical Trial

Official title:

Phase I Trial of Chemoradiation With Capecitabine and Vorinostat in Pancreatic Cancer.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00983268
• Other study ID #: VICC GI 0934
• Secondary ID: P30CA068485VU-VI
• Status: Completed
• Phase: Phase 1
• First received: September 23, 2009
• Last updated: June 11, 2015
• Start date: October 2009
• Est. completion date: February 2013

Study information

• Verified date: June 2015
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 ß-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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Cancer
• Pancreatic Neoplasms
• Periampullary Adenocarcinoma

Intervention

Drug:
• capecitabine
1000 mg taken by mouth on the days of radiation only.
• 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.

Locations

Country	Name	City	State
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee

Sponsors (3)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center	National Cancer Institute (NCI), National Comprehensive Cancer Network

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of vorinostat when given in combination with capecitabine and radiotherapy		Two weeks after completing radiotherapy	Yes
Secondary	Toxicity as assessed by NCI CTCAE v3.0		Six weeks after completing chemo-radiation therpay	Yes
Secondary	Tumor response as assessed by RECIST criteria		Six weeks after completing chemo-radiation therpay	No
Secondary	Biological effect		Six weeks after completing chemo-radiation therapy	No

External Links

•   Vanderbilt-Ingram Cancer Center, Find a Clinical Trial