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

Primary Purpose

Pancreatic Cancer, Adenocarcinoma of the Pancreas

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Radiation therapy
5-FU
Vorinostat
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring Zolinza

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Massachusetts General Hospital
  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vorinostat, 5-FU, Radiation Therapy

Arm Description

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)

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Progression Free Survival
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
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
Percentage of participants still alive at 1 year after enrollment on study
Response Rate
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
Percentage of patients able to undergo surgical resection after protocol therapy.

Full Information

First Posted
July 27, 2009
Last Updated
March 30, 2017
Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT00948688
Brief Title
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

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Terminated
Why Stopped
Funding was withdrawn after only 10 participants were enrolled
Study Start Date
August 2009 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
November 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer, Adenocarcinoma of the Pancreas
Keywords
Zolinza

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vorinostat, 5-FU, Radiation Therapy
Arm Type
Experimental
Arm Description
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)
Intervention Type
Radiation
Intervention Name(s)
Radiation therapy
Intervention Description
Once per day, 5 days a week for 6 weeks
Intervention Type
Drug
Intervention Name(s)
5-FU
Other Intervention Name(s)
Efudex, Carac, Fluoroplex, Adrucil
Intervention Description
Intravenously over 24 hours, 7 days per week during each week of radiation therapy
Intervention Type
Drug
Intervention Name(s)
Vorinostat
Other Intervention Name(s)
Zolinza
Intervention Description
Taken orally. Dose will depend upon time of enrollment and how well previous participants tolerated the drug
Primary Outcome Measure Information:
Title
Maximally Tolerated Dose (MTD) of Vorinostat in Combination With Infusional 5-FU and Radiation Therapy.
Description
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.
Time Frame
6 weeks
Title
Progression Free Survival (PFS) at 7 Months From Registration
Description
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.
Time Frame
7 months
Secondary Outcome Measure Information:
Title
Progression Free Survival
Description
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.
Time Frame
2 years
Title
Number of Participants Experiencing Unacceptable Toxicity
Description
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.
Time Frame
1 year
Title
Overall Survival
Description
Percentage of participants still alive at 1 year after enrollment on study
Time Frame
1 year
Title
Response Rate
Description
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%).
Time Frame
1 year
Title
Resectability Rate
Description
Percentage of patients able to undergo surgical resection after protocol therapy.
Time Frame
5 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lawrence Blaszkowsky, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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