Text Size

A Crossover Study to Assess the Effects of Vorinostat (MK0683, SAHA) in Patients With Advanced Cancer

This study has been completed.
Sponsor:
Information provided by:
Merck
ClinicalTrials.gov Identifier:
NCT00632931
First received: February 29, 2008
Last updated: April 21, 2010
Last verified: April 2010
History of Changes
Results First Received: January 18, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Single Blind (Subject);   Primary Purpose: Treatment
Conditions: Advanced Cancer Relapsed
Advanced Cancer Refractory
Interventions: Drug: vorinostat
Drug: Comparator: placebo (unspecified)

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

Eric Rubin, M.D., The Cancer Institute of New Jersey, New Brunswick, New Jersey; Pamela Munster, M.D., H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; Prof. Dr. Simon van Belle, University Hospital of Ghent, Ghent, Belgium.

Dosing initiated on 16-Jul-2007 and completed on 05-Feb-2009.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Enrolled patients were assigned to 1 of 2 dose sequences (vorinostat then placebo or placebo then vorinostat) in Part 1 of the study to determine the effect of vorinostat on the QTcF (Fridericia-corrected QT) interval. Following Part 1, active patients continued into Part 2, daily dosing of vorinostat.

Reporting Groups
  Description
Vorinostat Then Placebo: Part 1 Single dose 800 mg vorinostat in Period 1 followed by a three day wash out period, then matching placebo in Period 2. Following the last dose of study drug, there was a minimum 5 day washout before entering Part 2.
Placebo Then Vorinostat: Part 1 Single dose matching placebo in Period 1 followed by a three day wash out period, then single dose 800 mg vorinostat in Period 2. Following the last dose of study drug, there was a minimum 5 day washout before entering Part 2.
All Participants: Part 2 Vorinostat 400 mg once daily. Ten participants changed dosage to vorinostat 300 mg daily during Part 2.

Participant Flow for 5 periods

 Period 1:   Part 1, Period 1
    Vorinostat Then Placebo: Part 1     Placebo Then Vorinostat: Part 1     All Participants: Part 2  
STARTED     13     12     0  
COMPLETED     11     12     0  
NOT COMPLETED     2     0     0  
Protocol Violation                 1                 0                 0  
Withdrawal by Subject                 1                 0                 0  

Period 2:   Part 1, Washout
    Vorinostat Then Placebo: Part 1     Placebo Then Vorinostat: Part 1     All Participants: Part 2  
STARTED     11     12     0  
COMPLETED     11     12     0  
NOT COMPLETED     0     0     0  

Period 3:   Part 1, Period 2
    Vorinostat Then Placebo: Part 1     Placebo Then Vorinostat: Part 1     All Participants: Part 2  
STARTED     11     12     0  
COMPLETED     11     12     0  
NOT COMPLETED     0     0     0  

Period 4:   Post-Part 1 Washout
    Vorinostat Then Placebo: Part 1     Placebo Then Vorinostat: Part 1     All Participants: Part 2  
STARTED     12 [1]   12     0  
COMPLETED     12     12     0  
NOT COMPLETED     0     0     0  
[1] 1 patient who did not complete Period 1 was subsequently enrolled into Post Part 1

Period 5:   Part 2
    Vorinostat Then Placebo: Part 1     Placebo Then Vorinostat: Part 1     All Participants: Part 2  
STARTED     0     0     24  
COMPLETED     0     0     0  
NOT COMPLETED     0     0     24  
Adverse Event                 0                 0                 3  
Death                 0                 0                 1  
Lack of Efficacy                 0                 0                 17  
Withdrawal by Subject                 0                 0                 3  



  Baseline Characteristics
  Hide Baseline Characteristics

Reporting Groups
  Description
All Participants All Participants group includes data from all participants throughout Part 1 and Part 2 of the study.

Baseline Measures
    All Participants  
Number of Participants  
[units: participants]
 		  25  
Age  
[units: years]
Mean ( Full Range ) 		  59.4  
  ( 29 to 78 )  
Gender  
[units: participants]
 		 
Female     12  
Male     13  
Race/Ethnicity, Customized  
[units: participants]
 		 
Asian     1  
Black     2  
Hispanic     1  
White     21  
Cancer Type  
[units: Participants]
 		 
Ovarian     5  
Colon     3  
Lung     3  
Mesothelioma     3  
Uterine     2  
Soft Tissue     2  
Anal     1  
Basocellular     1  
Breast     1  
Gastrointestinal     1  
Mucinous carcinoma     1  
Pancreatic     1  
Thyroid     1  
Eastern Cooperative Oncology Group (ECOG) Performance Status [1]
[units: Participants]
 		 
0 = Normal Activity     9  
1 = Symptoms, but ambulatory     13  
2 = In bed <50% of the time     3  
Number of Prior Radiation Therapies  
[units: Participants]
 		 
None     14  
One Prior Radiation Therapy     7  
Two Prior Radiation Therapies     1  
Three or More Prior Radiation Therapies     3  
Number of Prior Systemic Anti-Cancer Therapies  
[units: Participants]
 		 
One Prior Systemic Anti-Cancer Therapy     0  
Two Prior Systemic Anti-Cancer Therapies     3  
Three or more Prior Systemic Anti-Cancer Therapies     22  
[1] ECOG Scale: 0 = Normal Activity, 1 = Symptoms, but ambulatory, 2 = In bed <50% of the time, 3 = In bed >50% of the time, 4 = 100% Bedridden, 5 = Dead



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Change From Baseline in QTcF at 0.5 Hours   [ Time Frame: Baseline and 0.5 hours ]

Measure Type Primary
Measure Title Change From Baseline in QTcF at 0.5 Hours
Measure Description The Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The change from baseline in QTcF was calculated by subtracting the QTcF value at each timepoint from the QTcF baseline (predose) value.
Time Frame Baseline and 0.5 hours  
Safety Issue Yes  

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.
All patients as treated population in Part 1 of the Study; 22 patients had QTcF data from the vorinostat period (One patient with protocol violation, and two patients without predose measurements were excluded) and 23 patients had QTcF data from the placebo period (one patient with protocol violation and one patient who discontinued were excluded)

Reporting Groups
  Description
Vorinostat No text entered.
Placebo No text entered.

Measured Values
    Vorinostat     Placebo  
Number of Participants Analyzed  
[units: participants]
 		  23     22  
Change From Baseline in QTcF at 0.5 Hours  
[units: milliseconds]
Mean ( 95% Confidence Interval ) 		  1.78  
  ( -1.53 to 5.09 )   		  -1.22  
  ( -4.53 to 2.08 )  


Statistical Analysis 1 for Change From Baseline in QTcF at 0.5 Hours
Groups [1] All groups
Mean Difference (Final Values) [2] 3.00
90% Confidence Interval ( -0.28 to 6.28 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



2.  Primary:   Change From Baseline in QTcF at 1 Hour   [ Time Frame: Baseline and 1 hour ]

Measure Type Primary
Measure Title Change From Baseline in QTcF at 1 Hour
Measure Description Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The change from baseline in QTcF was calculated by subtracting the QTcF value at each timepoint from the QTcF baseline (predose) value.
Time Frame Baseline and 1 hour  
Safety Issue Yes  

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.
All patients as treated population in Part 1 of the Study; 22 patients had QTcF data from the vorinostat period (One patient with protocol violation, and two patients without predose measurements were excluded) and 23 patients had QTcF data from the placebo period (one patient with protocol violation and one patient who discontinued were excluded)

Reporting Groups
  Description
Vorinostat No text entered.
Placebo No text entered.

Measured Values
    Vorinostat     Placebo  
Number of Participants Analyzed  
[units: participants]
 		  23     22  
Change From Baseline in QTcF at 1 Hour  
[units: milliseconds]
Mean ( 95% Confidence Interval ) 		  0.22  
  ( -3.09 to 3.52 )   		  -1.23  
  ( -4.54 to 2.08 )  


Statistical Analysis 1 for Change From Baseline in QTcF at 1 Hour
Groups [1] All groups
Mean Difference (Final Values) [2] 1.45
90% Confidence Interval ( -1.38 to 4.72 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



3.  Primary:   Change From Baseline in QTcF at 2 Hours   [ Time Frame: Baseline and 2 hours ]

Measure Type Primary
Measure Title Change From Baseline in QTcF at 2 Hours
Measure Description The Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The change from baseline in QTcF was calculated by subtracting the QTcF value at each timepoint from the QTcF baseline (predose) value.
Time Frame Baseline and 2 hours  
Safety Issue Yes  

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.
All patients as treated population in Part 1 of the Study; 22 patients had QTcF data from the vorinostat period (One patient with protocol violation, and two patients without predose measurements were excluded) and 23 patients had QTcF data from the placebo period (one patient with protocol violation and one patient who discontinued were excluded)

Reporting Groups
  Description
Vorinostat No text entered.
Placebo No text entered.

Measured Values
    Vorinostat     Placebo  
Number of Participants Analyzed  
[units: participants]
 		  23     23  
Change From Baseline in QTcF at 2 Hours  
[units: milliseconds]
Mean ( 95% Confidence Interval ) 		  1.09  
  ( -2.22 to 4.40 )   		  -1.98  
  ( -5.23 to 1.28 )  


Statistical Analysis 1 for Change From Baseline in QTcF at 2 Hours
Groups [1] All groups
Mean Difference (Final Values) [2] 3.07
90% Confidence Interval ( -0.17 to 6.31 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



4.  Primary:   Change From Baseline in QTcF at 3 Hours   [ Time Frame: Baseline and 3 hours ]

Measure Type Primary
Measure Title Change From Baseline in QTcF at 3 Hours
Measure Description The Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The change from baseline in QTcF was calculated by subtracting the QTcF value at each timepoint from the QTcF baseline (predose) value.
Time Frame Baseline and 3 hours  
Safety Issue Yes  

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.
All patients as treated population in Part 1 of the Study; 22 patients had QTcF data from the vorinostat period (One patient with protocol violation, and two patients without predose measurements were excluded) and 23 patients had QTcF data from the placebo period (one patient with protocol violation and one patient who discontinued were excluded)

Reporting Groups
  Description
Vorinostat No text entered.
Placebo No text entered.

Measured Values
    Vorinostat     Placebo  
Number of Participants Analyzed  
[units: participants]
 		  23     23  
Change From Baseline in QTcF at 3 Hours  
[units: milliseconds]
Mean ( 95% Confidence Interval ) 		  1.32  
  ( -1.99 to 4.63 )   		  -1.52  
  ( -4.77 to 1.73 )  


Statistical Analysis 1 for Change From Baseline in QTcF at 3 Hours
Groups [1] All groups
Mean Difference (Final Values) [2] 2.84
90% Confidence Interval ( -0.40 to 6.08 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



5.  Primary:   Change From Baseline in QTcF at 4 Hours   [ Time Frame: Baseline and 4 hours ]

Measure Type Primary
Measure Title Change From Baseline in QTcF at 4 Hours
Measure Description The Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The placebo-corrected change from baseline in QTcF was calculated by subtracting the QTcF change from baseline for placebo at each timepoint from the QTcF change from baseline for vorinostat at each timepoint.
Time Frame Baseline and 4 hours  
Safety Issue Yes  

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.
All patients as treated population in Part 1 of the Study; 22 patients had QTcF data from the vorinostat period (One patient with protocol violation, and two patients without predose measurements were excluded) and 23 patients had QTcF data from the placebo period (one patient with protocol violation and one patient who discontinued were excluded)

Reporting Groups
  Description
Vorinostat No text entered.
Placebo No text entered.

Measured Values
    Vorinostat     Placebo  
Number of Participants Analyzed  
[units: participants]
 		  23     23  
Change From Baseline in QTcF at 4 Hours  
[units: milliseconds]
Mean ( 95% Confidence Interval ) 		  4.95  
  ( 1.64 to 8.26 )   		  -1.49  
  ( -4.75 to 1.76 )  


Statistical Analysis 1 for Change From Baseline in QTcF at 4 Hours
Groups [1] All groups
Mean Difference (Final Values) [2] 6.44
90% Confidence Interval ( 3.21 to 9.68 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



6.  Primary:   Change From Baseline in QTcF at 8 Hours   [ Time Frame: Baseline and 8 hours ]

Measure Type Primary
Measure Title Change From Baseline in QTcF at 8 Hours
Measure Description The Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The change from baseline in QTcF was calculated by subtracting the QTcF value at each timepoint from the QTcF baseline (predose) value.
Time Frame Baseline and 8 hours  
Safety Issue Yes  

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.
All patients as treated population in Part 1 of the Study; 22 patients had QTcF data from the vorinostat period (One patient with protocol violation, and two patients without predose measurements were excluded) and 23 patients had QTcF data from the placebo period (one patient with protocol violation and one patient who discontinued were excluded)

Reporting Groups
  Description
Vorinostat No text entered.
Placebo No text entered.

Measured Values
    Vorinostat     Placebo  
Number of Participants Analyzed  
[units: participants]
 		  23     22  
Change From Baseline in QTcF at 8 Hours  
[units: milliseconds]
Mean ( 95% Confidence Interval ) 		  -3.56  
  ( -6.87 to -0.25 )   		  -7.89  
  ( -11.20 to -4.58 )  


Statistical Analysis 1 for Change From Baseline in QTcF at 8 Hours
Groups [1] All groups
Mean Difference (Final Values) [2] 4.33
90% Confidence Interval ( 1.05 to 7.60 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



7.  Primary:   Change From Baseline in QTcF at 12 Hours   [ Time Frame: Baseline and 12 hours ]

Measure Type Primary
Measure Title Change From Baseline in QTcF at 12 Hours
Measure Description The Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The change from baseline in QTcF was calculated by subtracting the QTcF value at each timepoint from the QTcF baseline (predose) value.
Time Frame Baseline and 12 hours  
Safety Issue Yes  

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.
All patients as treated population in Part 1 of the Study; 22 patients had QTcF data from the vorinostat period (One patient with protocol violation, and two patients without predose measurements were excluded) and 23 patients had QTcF data from the placebo period (one patient with protocol violation and one patient who discontinued were excluded)

Reporting Groups
  Description
Vorinostat No text entered.
Placebo No text entered.

Measured Values
    Vorinostat     Placebo  
Number of Participants Analyzed  
[units: participants]
 		  21     22  
Change From Baseline in QTcF at 12 Hours  
[units: milliseconds]
Mean ( 95% Confidence Interval ) 		  1.35  
  ( -2.08 to 4.78 )   		  -1.31  
  ( -4.62 to 2.00 )  


Statistical Analysis 1 for Change From Baseline in QTcF at 12 Hours
Groups [1] All groups
Mean Difference (Final Values) [2] 2.66
90% Confidence Interval ( -0.70 to 6.02 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



8.  Primary:   Change From Baseline in QTcF at 24 Hours   [ Time Frame: Baseline and 24 hours ]

Measure Type Primary
Measure Title Change From Baseline in QTcF at 24 Hours
Measure Description The Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The change from baseline in QTcF was calculated by subtracting the QTcF value at each timepoint from the QTcF baseline (predose) value.
Time Frame Baseline and 24 hours  
Safety Issue Yes  

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.
All patients as treated population in Part 1 of the Study; 22 patients had QTcF data from the vorinostat period (One patient with protocol violation, and two patients without predose measurements were excluded) and 23 patients had QTcF data from the placebo period (one patient with protocol violation and one patient who discontinued were excluded)

Reporting Groups
  Description
Vorinostat No text entered.
Placebo No text entered.

Measured Values
    Vorinostat     Placebo  
Number of Participants Analyzed  
[units: participants]
 		  22     22  
Change From Baseline in QTcF at 24 Hours  
[units: milliseconds]
Mean ( 95% Confidence Interval ) 		  1.53  
  ( -1.84 to 4.98 )   		  -4.89  
  ( -8.29 to -1.67 )  


Statistical Analysis 1 for Change From Baseline in QTcF at 24 Hours
Groups [1] All groups
Mean Difference (Final Values) [2] 6.51
90% Confidence Interval ( 3.19 to 9.82 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.




  Serious Adverse Events
  Show Serious Adverse Events


  Other Adverse Events
  Show Other Adverse Events


  More Information
  Hide More Information

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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
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.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: Executive Vice President, Clinical and Quantitative Sciences
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372


No publications provided


Responsible Party: Executive Vice President, Clinical and Quantitative Sciences, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier: NCT00632931     History of Changes
Other Study ID Numbers: 2008_515, MK0683-070
Study First Received: February 29, 2008
Results First Received: January 18, 2010
Last Updated: April 21, 2010
Health Authority: United States: Food and Drug Administration