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Vorinostat, Carboplatin and Gemcitabine in Women With Recurrent, Platinum-Sensitive Ovarian Cancer

This study has been terminated.
(Terminated due to unacceptable toxicity)
Sponsor:
Collaborators:
Brigham and Women's Hospital
Massachusetts General Hospital
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Ursula A. Matulonis, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00910000
First received: May 26, 2009
Last updated: August 10, 2016
Last verified: August 2016
Results First Received: March 29, 2016  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Interventions: Drug: Vorinostat
Drug: Carboplatin
Drug: Gemcitabine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
15 participants were enrolled and treated between July 2009 and January 2013. One patient excluded from all analyses failed screening after consent because of elevated liver function tests and did not receive treatment.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Dose Level 1A

Vorinostat: 200 mg taken orally once a day for the first two weeks of each three-week cycle

Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle

Gemcitabine: 100 mg/m2, given intravenously on day 1 and day 8 of every three week cycle

Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.

Dose Level 2A

Vorinostat: 300mg, taken orally once a day for the first two weeks of each three-week cycle

Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle

Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle

Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.

Dose Level 1B

Vorinostat: 200mg, taken orally twice a day for days 1-3 and days 8-10 of every three week cycle

Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle

Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle

Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.

Dose Level 1C

Vorinostat: 200mg, taken orally twice a day for days 1, 2, 8 and 9 of every three week cycle

Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle

Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle

Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.

Dose Level 1D

Vorinostat: 300mg, taken orally once a day for days 1 and 2 of every three week cycle

Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle

Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle

Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.

Dose Level 2D

Vorinostat: 400mg, taken orally once a day for days 1 and 2 of every three week cycle

Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle

Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle

Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.


Participant Flow:   Overall Study
    Dose Level 1A   Dose Level 2A   Dose Level 1B   Dose Level 1C   Dose Level 1D   Dose Level 2D
STARTED   3   3   3   2   3   1 
COMPLETED   3   0   0   0   2   0 
NOT COMPLETED   0   3   3   2   1   1 
Adverse Event                0                3                2                2                0                1 
Withdrawal by Subject                0                0                1                0                1                0 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Dose Level 1A

Vorinostat: 200 mg taken orally once a day for the first two weeks of each three-week cycle

Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle

Gemcitabine: 100 mg/m2, given intravenously on day 1 and day 8 of every three week cycle

Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.

Dose Level 2A

Vorinostat: 300mg, taken orally once a day for the first two weeks of each three-week cycle

Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle

Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle

Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.

Dose Level 1B

Vorinostat: 200mg, taken orally twice a day for days 1-3 and days 8-10 of each three-week cycle

Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle

Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle

Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.

Dose Level 1C

Vorinostat: 200mg, taken orally twice a day for days 1, 2, 8 and 9 of each three-week cycle

Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle

Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle

Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.

Dose Level 1D

Vorinostat: 300mg, taken orally once a day for days 1 and 2 of each three-week cycle

Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle

Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle

Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.

Dose Level 2D

Vorinostat: 400mg, taken orally once a day for days 1 and 2 of each three-week cycle

Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle

Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle

Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.

Total Total of all reporting groups

Baseline Measures
   Dose Level 1A   Dose Level 2A   Dose Level 1B   Dose Level 1C   Dose Level 1D   Dose Level 2D   Total 
Overall Participants Analyzed 
[Units: Participants]
 3   3   3   2   3   1   15 
Age, Customized [1] 
[Units: Years]
Mean (Full Range)
             
Age   59 
 (51 to 68) 
 63 
 (61 to 65) 
 59 
 (54 to 66) 
 54.5 
 (52 to 57) 
 67 
 (58 to 75) 
 63 [1]   60 
 (51 to 75) 
[1] There is only 1 patient in this cohort.
Gender 
[Units: Participants]
             
Female   3   3   3   2   3   1   15 
Male   0   0   0   0   0   0   0 
Region of Enrollment 
[Units: Participants]
             
United States   3   3   3   2   3   1   15 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Vorinostat Maximum Tolerated Dose (MTD) [Phase Ib]   [ Time Frame: The DLT observation period in determining the MTD was the 21-day cycle 1 length. ]

2.  Primary:   Dose Limiting Toxicity (DLT) [Phase Ib]   [ Time Frame: The DLT observation period in determining the MTD was the 21-day cycle 1 length. ]

3.  Secondary:   Response   [ Time Frame: Disease was assessed radiographically (CT or MRI scan) every 2 cycles on treatment; Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8). ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study was terminated early for toxicities and the emergence of better tolerated and more promising biologic agents added to platinum-based chemotherapy and/or use as maintenance.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Ursula Matulonis, MD
Organization: Dana-Farber Cancer Institute
phone: 617-632-2334
e-mail: umatulonis@partners.org


Publications of Results:

Responsible Party: Ursula A. Matulonis, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00910000     History of Changes
Other Study ID Numbers: 09-026
Study First Received: May 26, 2009
Results First Received: March 29, 2016
Last Updated: August 10, 2016
Health Authority: United States: Food and Drug Administration