Clinical trial NCT00948688: Vorinostat With XRT and 5-FU for Locally Advanced Adenocarcinoma of the Pancreas
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer
Adenocarcinoma of the Pancreas
Keywords: Zolinza
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Dana-Farber Cancer Institute
name: Brigham and Women's Hospital
name: Merck Sharp & Dohme LLC
First posted: 2009-07-29
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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)

Primary outcomes:
measure: Maximally Tolerated Dose (MTD) of Vorinostat in Combination With Infusional 5-FU and Radiation Therapy.
timeFrame: 6 weeks
measure: Progression Free Survival (PFS) at 7 Months From Registration
timeFrame: 7 months
Secondary outcomes:
measure: Progression Free Survival
timeFrame: 2 years
measure: Number of Participants Experiencing Unacceptable Toxicity
timeFrame: 1 year
measure: Overall Survival
timeFrame: 1 year
measure: Response Rate
timeFrame: 1 year
measure: Resectability Rate
timeFrame: 5 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Lawrence Blaszkowsky, MD
role: PRINCIPAL_INVESTIGATOR
References: