Vorinostat in Combination With Radiation Therapy and Infusional Fluorouracil (5-FU) in Patients With Locally Advanced Adenocarcinoma of the Pancreas - Full Text View

Sponsor:	Massachusetts General Hospital
Collaborators:	Dana-Farber Cancer Institute Brigham and Women's Hospital Merck
Information provided by (Responsible Party):	Lawrence S. Blaszkowsky, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00948688

Purpose

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.

Condition	Intervention	Phase
Pancreatic Cancer Adenocarcinoma of the Pancreas	Radiation: Radiation therapy Drug: 5-FU Drug: Vorinostat	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase 1/2 Study of Vorinostat in Combination With Radiation Therapy and Infusional 5-FU in Patients With Locally Advanced Adenocarcinoma of the Pancreas

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Fluorouracil Pancrelipase Vorinostat

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

Determine the maximally tolerated dose (MTD) and tolerability of vorinostat in combination with infusional 5-FU and radiation therapy. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Progression free survival at 7 months from registration [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Determine progression free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Determine toxicity profile [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Median survival, response rate and resectability rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	August 2009
Estimated Study Completion Date:	August 2013
Estimated Primary Completion Date:	August 2012 (Final data collection date for primary outcome measure)

Intervention Details:

Once per day, 5 days a week for 6 weeks

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

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

Other Name: Zolinza

Detailed Description:

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.

Eligibility

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

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00948688

Locations

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Massachusetts General Hospital

Dana-Farber Cancer Institute

Brigham and Women's Hospital

Merck

Investigators

Principal Investigator:

Lawrence Blaszkowsky, MD

Massachusetts General Hospital

More Information

No publications provided

Responsible Party:	Lawrence S. Blaszkowsky, MD, Assistant Physician, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00948688 History of Changes
Other Study ID Numbers:	09-114
Study First Received:	July 27, 2009
Last Updated:	April 25, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:

Zolinza

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
Fluorouracil
Vorinostat

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

ClinicalTrials.gov processed this record on May 24, 2012