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

Condition(s) targeted: Pancreatic Cancer; Adenocarcinoma of the Pancreas

Intervention: Radiation therapy (Radiation); 5-FU (Drug); Vorinostat (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Massachusetts General Hospital

Official(s) and/or principal investigator(s):
Lawrence Blaszkowsky, MD, Principal Investigator, Affiliation: Massachusetts General Hospital

Overall contact:
Lawrence Blaszkowsky, MD, Phone: 617-724-4637, Email: lblaszkowsky@partners.org

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.

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

Study design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety Study

Primary outcome:

Determine the maximally tolerated dose (MTD) and tolerability of vorinostat in combination with infusional 5-FU and radiation therapy.

Progression free survival at 7 months from registration

Secondary outcome:

Determine progression free survival

Determine toxicity profile

Median survival, response rate and resectability rate

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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)

Lawrence Blaszkowsky, MD, Phone: 617-724-4637, Email: lblaszkowsky@partners.org

Massachusetts General Hospital, Boston, Massachusetts 02114, United States; Recruiting
Lawrence Blaszkowsky, MD, Principal Investigator

Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States; Recruiting
Brian Wolpin, MD, Principal Investigator

Starting date: August 2009
Last updated: August 27, 2009