Phase I-II Study of Vorinostat, Paclitaxel, and Bevacizumab in Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00368875
First received: August 24, 2006
Last updated: October 6, 2015
Last verified: March 2014
Results First Received: June 18, 2015  
Study Type: Interventional
Study Design: Endpoint Classification: Safety Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Male Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Interventions: Drug: vorinostat
Drug: paclitaxel
Biological: bevacizumab

  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
Between July 2006 and December 2009 a total of 54 patients were registered on the study.

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
Phase I

Vorinostat dose (200 or 300 mg BID) was assigned at the time of registration. Vorinostat was administered orally twice daily on days 1–3, 8–10, and 15–17 of each 28-day cycle.

All patients also received paclitaxel at 90 mg/m2 as 1-hour infusion on days 2, 9, and 16 of every 28-day cycle. Bevacizumab was administered on day 2 and day 16 of the 28 day cycle at 10 mg/kg dose. Vorinostat dose escalation was carried out in the standard 3 + 3 phase I trial design based upon toxicity observed during the first cycle of therapy.

Phase II

Vorinostat was administered orally twice daily at the recommended phase II dose of 300 mg on days 1–3, 8–10, and 15–17 of each 28-day cycle.

All patients also received paclitaxel at 90 mg/m2 as 1-hour infusion on days 2, 9, and 16 of every 28-day cycle. Bevacizumab was administered on day 2 and day 16 of the 28 day cycle at 10 mg/kg dose.


Participant Flow:   Overall Study
    Phase I     Phase II  
STARTED     6     48  
COMPLETED     0     0  
NOT COMPLETED     6     48  
Adverse Event                 0                 12  
Progressive disease                 3                 27  
Withdrawal by Subject                 2                 6  
Other Reason                 0                 2  
Alternative Therapy                 1                 1  



  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
Phase I + Phase II

Phase I: Vorinostat dose (200 or 300 mg BID) was assigned at the time of registration. Vorinostat was administered orally twice daily on days 1–3, 8–10, and 15–17 of each 28-day cycle.

All patients also received paclitaxel at 90 mg/m2 as 1-hour infusion on days 2, 9, and 16 of every 28-day cycle. Bevacizumab was administered on day 2 and day 16 of the 28 day cycle at 10 mg/kg dose. Vorinostat dose escalation was carried out in the standard 3 + 3 phase I trial design based upon toxicity observed during the first cycle of therapy.

Phase II: Vorinostat was administered orally twice daily at the recommended phase II dose of 300 mg on days 1–3, 8–10, and 15–17 of each 28-day cycle.

All patients also received paclitaxel at 90 mg/m2 as 1-hour infusion on days 2, 9, and 16 of every 28-day cycle. Bevacizumab was administered on day 2 and day 16 of the 28 day cycle at 10 mg/kg dose.


Baseline Measures
    Phase I + Phase II  
Number of Participants  
[units: participants]
  54  
Age  
[units: years]
Median (Full Range)
  54  
  (27 to 77)  
Gender  
[units: participants]
 
Female     54  
Male     0  
Race/Ethnicity, Customized  
[units: participants]
 
White     37  
Black     11  
Asian     2  
Unknown     4  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Recommended Phase II Dose as Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Phase I)   [ Time Frame: 28 days ]

2.  Primary:   Objective Response Rate (CR + PR)   [ Time Frame: Up to 12 months ]

3.  Secondary:   Progression-free Survival (PFS),   [ Time Frame: From first treatment day until objective or symptomatic progression, assessed up to 12 months ]

4.  Secondary:   Time to Treatment Failure (TTF)   [ Time Frame: Time from the first treatment day until disease progression or discontinuation of treatment due to toxicity, assessed up to 12 months ]

5.  Secondary:   Overall Survival(OS)   [ Time Frame: Time from first treatment day until death, assessed up to 12 months ]


  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
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  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: NYCC Regulatory Coordinator
Organization: Montefiore Medical Center - New York
phone: 718-379-6862
e-mail: sforde@montefiore.org


Publications of Results:

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00368875     History of Changes
Other Study ID Numbers: NCI-2012-03012
NCI-2012-03012 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
06-05-291 ( Other Identifier: Montefiore Medical Center )
7703 ( Other Identifier: CTEP )
N01CM62204 ( US NIH Grant/Contract Award Number )
N01CM62207 ( US NIH Grant/Contract Award Number )
N01CM62205 ( US NIH Grant/Contract Award Number )
N01CM62209 ( US NIH Grant/Contract Award Number )
Study First Received: August 24, 2006
Results First Received: June 18, 2015
Last Updated: October 6, 2015
Health Authority: United States: Food and Drug Administration