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

Primary Purpose

Pancreatic Cancer, Periampullary Adenocarcinoma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

capecitabine

vorinostat

Radiotherapy

Surgery to remove tumor

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring periampullary adenocarcinoma, stage I pancreatic cancer, stage II pancreatic cancer, stage III pancreatic cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Vanderbilt-Ingram Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment Arm

Arm Description

Outcomes

Primary Outcome Measures

Maximum tolerated dose of vorinostat when given in combination with capecitabine and radiotherapy

Secondary Outcome Measures

Toxicity as assessed by NCI CTCAE v3.0

Tumor response as assessed by RECIST criteria

Biological effect

Full Information

NCT ID

NCT00983268

First Posted

September 23, 2009

Last Updated

June 11, 2015

Sponsor

Vanderbilt-Ingram Cancer Center

Collaborators

National Cancer Institute (NCI), National Comprehensive Cancer Network

1. Study Identification

Unique Protocol Identification Number

NCT00983268

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2015

Overall Recruitment Status

Completed

Study Start Date

October 2009 (undefined)

Primary Completion Date

February 2013 (Actual)

Study Completion Date

February 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Vanderbilt-Ingram Cancer Center

Collaborators

National Cancer Institute (NCI), National Comprehensive Cancer Network

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreatic Cancer, Periampullary Adenocarcinoma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment Arm

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

capecitabine

Intervention Description

1000 mg taken by mouth on the days of radiation only.

Intervention Type

Drug

Intervention Name(s)

vorinostat

Intervention Description

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

Intervention Type

Radiation

Intervention Name(s)

Radiotherapy

Intervention Description

High-dose hypofractionated radiotherapy consisting of 3000 cGy in 10 fractions, Monday-Friday for 2 weeks.

Intervention Type

Procedure

Intervention Name(s)

Surgery to remove tumor

Intervention Description

Patients will be assessed for resectability within six weeks of the end of chemoradiation, if resectable, surgery will be performed.

Primary Outcome Measure Information:

Title

Maximum tolerated dose of vorinostat when given in combination with capecitabine and radiotherapy

Time Frame

Two weeks after completing radiotherapy

Secondary Outcome Measure Information:

Title

Toxicity as assessed by NCI CTCAE v3.0

Time Frame

Six weeks after completing chemo-radiation therpay

Title

Tumor response as assessed by RECIST criteria

Time Frame

Six weeks after completing chemo-radiation therpay

Title

Biological effect

Time Frame

Six weeks after completing chemo-radiation therapy

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Emily Chan, M.D, Ph.D.

Organizational Affiliation

Vanderbilt-Ingram Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Vanderbilt-Ingram Cancer Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232-6838

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.vicc.org/ct/

Description

Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

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

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