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

NCT00948688 | Terminated Phase 1 Results DMC

• 1 other identifier: 09-114
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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.

Conditions

Pancreatic Cancer; Adenocarcinoma of the Pancreas

Keywords

Zolinza

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Progression Free Survival

  2 years

• Number of Participants Experiencing Unacceptable Toxicity

  1 year

• Overall Survival

  1 year

• Response Rate

  1 year

• Resectability Rate

  5 months

Study Arms (1)

Vorinostat, 5-FU, Radiation Therapy

EXPERIMENTAL

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; Drug: 5-FU; Drug: Vorinostat

Interventions

Radiation therapy RADIATION

Once per day, 5 days a week for 6 weeks

Vorinostat, 5-FU, Radiation Therapy

5-FU DRUG

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

Also known as: Efudex, Carac, Fluoroplex, Adrucil

Vorinostat, 5-FU, Radiation Therapy

Vorinostat DRUG

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

Also known as: Zolinza

Vorinostat, 5-FU, Radiation Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Dana-Farber Cancer Institute: collaborator
• Brigham and Women's Hospital: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Radiotherapy; Fluorouracil; Vorinostat

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Limitations and Caveats

Only 10 participants were enrolled on this trial that planned for 50. Phase II portion of the study was not reached and therefore endpoint analysis is severely limited by sample size.

Results Point of Contact

• Title: Lawrence S. Blaszkowsky, M.D.
• Organization: Massachusetts General Hospital

lblaszkowsky@mgh.harvard.edu

617-219-1230

Study Officials

• Lawrence Blaszkowsky, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Physician

Study Record Dates

• First Submitted: July 27, 2009
• First Posted: July 29, 2009
• Study Start: August 1, 2009
• Primary Completion: June 1, 2012
• Study Completion: November 1, 2013
• Last Updated: May 10, 2017
• Results First Posted: May 10, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)