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

Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00948688
• Other study ID #: 09-114
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: July 27, 2009
• Last updated: April 25, 2012
• Start date: August 2009
• Est. completion date: August 2013

Study information

• Verified date: April 2012
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: August 2013
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Pancreas
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Brigham and Women's Hospital, Dana-Farber Cancer Institute, Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the maximally tolerated dose (MTD) and tolerability of vorinostat in combination with infusional 5-FU and radiation therapy.		2 years	Yes
Primary	Progression free survival at 7 months from registration		2 years	No
Secondary	Determine progression free survival		2 years	No
Secondary	Determine toxicity profile		2 years	Yes
Secondary	Median survival, response rate and resectability rate		2 years	No