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Trial record 1 of 1 for:    NCT00948688
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Vorinostat With XRT and 5-FU for Locally Advanced Adenocarcinoma of the Pancreas

This study has been terminated.
(Funding was withdrawn after only 10 participants were enrolled)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00948688
First Posted: July 29, 2009
Last Update Posted: May 10, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Lawrence S. Blaszkowsky, MD, Massachusetts General Hospital
  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: Intervention Model: Single Group Assignment
Masking: None (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:


Further study details as provided by Lawrence S. Blaszkowsky, MD, Massachusetts General Hospital:

Primary Outcome Measures:
  • Maximally Tolerated Dose (MTD) of Vorinostat in Combination With Infusional 5-FU and Radiation Therapy. [ Time Frame: 6 weeks ]
    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.

  • Progression Free Survival (PFS) at 7 Months From Registration [ Time Frame: 7 months ]
    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.


Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: 2 years ]
    Progression free survival for this endpoint was defined as the duration of time from beginning of the patients' initial chemotherapy 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.

  • Number of Participants Experiencing Unacceptable Toxicity [ Time Frame: 1 year ]
    All participants who receive at least one dose of study treatment were evaluable for toxicity. Unacceptable toxicity is based on the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Most grade 3 (severe) or 4 (life-threatening) events are considered to be unacceptable toxicities -- exceptions include nausea or vomiting, fatigue, and alopecia. Hematologic toxicities need to be either grade 4 or last for protocol-defined durations to be considered unacceptable.

  • Overall Survival [ Time Frame: 1 year ]
    Percentage of participants still alive at 1 year after enrollment on study

  • Response Rate [ Time Frame: 1 year ]
    Participants who have either a complete response (disappearance of all target lesions), partial response (at least 30% decrease in sum of longest diameter of target lesions) or stable disease (decrease in size of less than 30% or increase in size of less than 20%).

  • Resectability Rate [ Time Frame: 5 months ]
    Percentage of patients able to undergo surgical resection after protocol therapy.


Enrollment: 10
Study Start Date: August 2009
Study Completion Date: November 2013
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vorinostat, 5-FU, Radiation Therapy
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
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
Other Name: Efudex, Carac, Fluoroplex, Adrucil
Drug: Vorinostat
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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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 Sharp & Dohme Corp.
Investigators
Principal Investigator: Lawrence Blaszkowsky, MD Massachusetts General Hospital
  More Information

Responsible Party: Lawrence S. Blaszkowsky, MD, Assistant Physician, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00948688     History of Changes
Other Study ID Numbers: 09-114
First Submitted: July 27, 2009
First Posted: July 29, 2009
Results First Submitted: January 27, 2017
Results First Posted: May 10, 2017
Last Update Posted: May 10, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Lawrence S. Blaszkowsky, MD, 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
Pancrelipase
Vorinostat
Gastrointestinal Agents
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action