Vorinostat With XRT And 5-FU For Locally Advanced Adenocarcinoma Of The Pancreas

Study Overview

Vorinostat With XRT and 5-FU for Locally Advanced Adenocarcinoma of the Pancreas

The durg vorinostat (Zolinza) is a type of drug called an histone deacetylase (HDAC) inhibitor. It inhibits a group of enzymes called histone deacetylases. These enzymes help cancer cells survive. By inhibiting these enzymes, vorinostat helps kill cancer cells. In this research study vorinostat will be given along with radiation therapy and the drug 5-FU. This is the first research study in which vorinostat will be given along with radiation therapy and 5-FU. The purpose of this research study is to find the highest dose of vorinostat that can be given safely along with radiation therapy and 5-FU. The investigators will also begin to get information about whether vorinostat combined with radiation and 5-FU may help to treat pancreatic cancer.

* Since we are looking for the highest dose of vorinostat that can be administered safely without severe or unmanageable side effects, not everyone who participates will receive the same dose. The dose will depend upon the number of participants enrolled on the study and how well they have tolerated their doses. * 5-FU will be given intravenously over 24 hours 7 days per week during each week of radiation therapy. In order for participants to be able to receive the 5-FU as an outpatient, they will need to have central line catheter placed. * Radiation therapy will be given once per day, 5 days per week, for 6 weeks. * Vorinostat is taken orally. * Participants will be seen once per week during the 6 weeks that they are receiving 5-FU, radiation therapy and vorinostat.

Pancreatic Cancer
Adenocarcinoma of the Pancreas

RADIATION: Radiation therapy
DRUG: 5-FU
DRUG: Vorinostat

09-114

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2009-07-27	Results First Submitted 2017-01-27	Last Update Submitted that met QC Criteria 2017-03-30
First Submitted that Met QC Criteria 2009-07-28	Results First Submitted that Met QC Criteria 2017-03-30	Last Update Posted (ACTUAL) 2017-05-10
First Posted (ACTUAL) 2009-07-29	Results First Posted 2017-05-10	Last Verified 2017-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Vorinostat, 5-FU, Radiation Therapy Vorinostat at varying doses; orally, days 1-7, weeks 1-6 5-FU 225 mg/m2/day; intravenous; days 1-5, weeks 1-6 until completion of radiation therapy; Radiation therapy; 180cGy daily Monday-Friday; 28 days of treatment (6 weeks)	RADIATION: Radiation therapy Once per day, 5 days a week for 6 weeks DRUG: 5-FU Intravenously over 24 hours, 7 days per week during each week of radiation therapy DRUG: Vorinostat Taken orally. Dose will depend upon time of enrollment and how well previous participants tolerated the drug

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Vorinostat, 5-FU, Radiation Therapy

Vorinostat at varying doses; orally, days 1-7, weeks 1-6 5-FU 225 mg/m2/day; intravenous; days 1-5, weeks 1-6 until completion of radiation therapy; Radiation therapy; 180cGy daily Monday-Friday; 28 days of treatment (6 weeks)

RADIATION: Radiation therapy

Once per day, 5 days a week for 6 weeks

DRUG: 5-FU

Intravenously over 24 hours, 7 days per week during each week of radiation therapy

DRUG: Vorinostat

Taken orally. Dose will depend upon time of enrollment and how well previous participants tolerated the drug

Primary Outcome Measures	Measure Description	Time Frame
Maximally Tolerated Dose (MTD) of Vorinostat in Combination With Infusional 5-FU and Radiation Therapy.	The maximum tolerated dose (MTD) is defined as one dose level below the dose level at which participants experience an unacceptable rate of dose-limiting toxicity.	6 weeks
Progression Free Survival (PFS) at 7 Months From Registration	Progression free survival was defined as the duration of time from registration on study to time of objective disease progression. Death was regarded as a progression event. Progression was defined by the Response Evaluation Criteria in Solid Tumors (RECIST) as at least a 20% increase in the sum of the longest diameter of target lesions, or the appearance of one or more new lesions as seen on radiologic evaluation.	7 months

Secondary Outcome Measures	Measure Description	Time Frame
Progression Free Survival	Progression free survival for this endpoint was defined as the duration of time from beginning of the patients' initial chemotherapy to time of objective disease progression. Death was regarded as a progression event. Progression was defined by the Response Evaluation Criteria in Solid Tumors (RECIST) as at least a 20% increase in the sum of the longest diameter of target lesions, or the appearance of one or more new lesions as seen on radiologic evaluation.	2 years
Number of Participants Experiencing Unacceptable Toxicity	All participants who receive at least one dose of study treatment were evaluable for toxicity. Unacceptable toxicity is based on the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Most grade 3 (severe) or 4 (life-threatening) events are considered to be unacceptable toxicities -- exceptions include nausea or vomiting, fatigue, and alopecia. Hematologic toxicities need to be either grade 4 or last for protocol-defined durations to be considered unacceptable.	1 year
Overall Survival	Percentage of participants still alive at 1 year after enrollment on study	1 year
Response Rate	Participants who have either a complete response (disappearance of all target lesions), partial response (at least 30% decrease in sum of longest diameter of target lesions) or stable disease (decrease in size of less than 30% or increase in size of less than 20%).	1 year
Resectability Rate	Percentage of patients able to undergo surgical resection after protocol therapy.	5 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically or cytologically proven adenocarcinoma of the pancreas
Evaluable disease
Must have received 3-4 months of gemcitabine-based chemotherapy and have had stable disease by RECIST criteria. Regimens include:

gemcitabine alone
gemcitabine and erlotinib
gemcitabine and oxaliplatin
gemcitabine and cisplatin
gemcitabine and capecitabine
18 years of age or older
Life expectancy of greater than 4 months
ECOG Performance Status 0-1
Normal organ and marrow function as outlined in the protocol
Ability to drink at least 2 liters of fluid daily
Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation
Patients must be able to swallow capsules

Chemotherapy within 3 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
Participants may not be receiving any other study agents
Known distant metastases to any organ
History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or 5-FU
Patients taking warfarin due to potential interactions of both 5-FU and vorinostat. Low molecular weight heparin should be substituted when appropriate
Patients who have received upper abdominal radiation therapy which fields would overlap with that determined necessary to treat the primary tumor.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant or breastfeeding women
Individuals with history of a different malignancy are ineligible unless they are deemed by the investigator to be at low risk of recurrence of that malignancy. Patients may not have a concurrent second malignancy.
Active HIV or hepatitis
Prior exposure to HDAC inhibitor (except valproic acid, provided there is a 30 day washout period)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Dana-Farber Cancer Institute
Brigham and Women's Hospital
Merck Sharp & Dohme LLC

Investigators

PRINCIPAL_INVESTIGATOR: Lawrence Blaszkowsky, MD, Massachusetts General Hospital

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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