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

This study has been completed.

Study NCT00632931 Information provided by Merck

First Received on February 29, 2008. Last Updated on April 21, 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

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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
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.

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
STARTED	13	12
COMPLETED	11	12
NOT COMPLETED	2	0
Protocol Violation	1	0
Withdrawal by Subject	1	0

Period 2: Part 1, Washout

	Vorinostat Then Placebo: Part 1	Placebo Then Vorinostat: Part 1
STARTED	11	12
COMPLETED	11	12
NOT COMPLETED	0	0

Period 3: Part 1, Period 2

	Vorinostat Then Placebo: Part 1	Placebo Then Vorinostat: Part 1
STARTED	11	12
COMPLETED	11	12
NOT COMPLETED	0	0

Period 4: Post-Part 1 Washout

	Vorinostat Then Placebo: Part 1	Placebo Then Vorinostat: Part 1
STARTED	12 ^[1]	12
COMPLETED	12	12
NOT COMPLETED	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

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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

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1. Primary:

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

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2. Primary:

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

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3. Primary:

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

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4. Primary:

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

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5. Primary:

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

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6. Primary:

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

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7. Primary:

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

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8. Primary:

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

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Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

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