A Clinical Trial of Vorinostat (MK0683, SAHA) in Combination With FDA Approved Cancer Drugs in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

This study has been terminated.

( The study was terminated based on the recommendation by the DSMB following a pre-planned protocol interim analysis because the endpoint was not achieved. )

Study NCT00473889 Information provided by Merck

First Received on May 14, 2007. Last Updated on April 20, 2010 History of Changes

Results First Received: September 3, 2009

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	Stage IIIB or IV Non-Small Cell Lung Cancer
Interventions:	Drug: vorinostat Drug: Comparator: paclitaxel Drug: Comparator: carboplatin Drug: Comparator: placebo

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
This study was conducted at 99 investigative sites worldwide. The first patient’s first visit was 16 May 07 and the last patient’s last visit was 12 Dec 2008.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Randomized participants were stratified by Stage (IIIB versus IV), geographic region and eligibility for treatment with bevacizumab prior to treatment assignment.

Reporting Groups

	Description
Vorinostat + Paclitaxel + Carboplatin	Experimental arm: Vorinostat capsules (400 mg) once daily on Days -4 through 10 of Cycle 1 (25 day treatment cycle) and Days 1 through 14 of each subsequent 21 day treatment cycle; paclitaxel (200 mg/m2) and carboplatin (area under concentration/time curve of 6 mg/min/mL) administered by intravenous (IV) infusion on Day 1 of each treatment cycle.
Placebo + Paclitaxel + Carboplatin	Placebo Comparator arm: Placebo capsules once daily on Days -4 through 10 of Cycle 1 (25 day treatment cycle) and Days 1 through 14 of each subsequent 21 day treatment cycle; paclitaxel (200 mg/m2) and carboplatin (area under concentration/time curve of 6 mg/min/mL) administered by intravenous (IV) infusion on Day 1 of each treatment cycle.

Participant Flow: Overall Study

	Vorinostat + Paclitaxel + Carboplatin	Placebo + Paclitaxel + Carboplatin
STARTED	126	127
COMPLETED	43	63
NOT COMPLETED	83	64
Did not receive study medication	1	4
Adverse Event	30	17
Protocol Violation	4	2
Lack of Efficacy	28	29
Lost to Follow-up	2	1
Physician Decision	10	5
Trial Terminated	3	6
Withdrawal by Subject	5	0

Baseline Characteristics

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Reporting Groups

	Description
Vorinostat + Paclitaxel + Carboplatin	Experimental arm: Vorinostat capsules (400 mg) once daily on Days -4 through 10 of Cycle 1 (25 day treatment cycle) and Days 1 through 14 of each subsequent 21 day treatment cycle; paclitaxel (200 mg/m2) and carboplatin (area under concentration/time curve of 6 mg/min/mL) administered by intravenous (IV) infusion on Day 1 of each treatment cycle.
Placebo + Paclitaxel + Carboplatin	Placebo Comparator arm: Placebo capsules once daily on Days -4 through 10 of Cycle 1 (25 day treatment cycle) and Days 1 through 14 of each subsequent 21 day treatment cycle; paclitaxel (200 mg/m2) and carboplatin (area under concentration/time curve of 6 mg/min/mL) administered by intravenous (IV) infusion on Day 1 of each treatment cycle.

Baseline Measures

	Vorinostat + Paclitaxel + Carboplatin	Placebo + Paclitaxel + Carboplatin	Total
Number of Participants [units: participants]	126	127	253
Age, Customized [units: participants]
Less Than 65 years	70	89	159
65 years or Older	56	38	94
Gender [units: participants]
Female	34	56	90
Male	92	71	163
Race/Ethnicity, Customized [units: participants]
White	79	79	158
Black	3	4	7
Asian	31	32	63
American Indian or Alaskan Native mix	13	12	25
Cancer Stage [units: Participants]
IIIB	14	15	29
IV	112	112	224
Eligibility to receive treatment with Bevacizumab [units: Participants]
Eligible	70	63	133
Ineligible	55	60	115
Unknown	1	4	5
Geographic region where the participant lived [units: Participants]
North America	25	27	52
Europe (United Kingdom, Italy, Germany, and Spain)	41	40	81
Asia	22	24	46
Rest of the World	38	36	74

Outcome Measures

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1. Primary:

Overall Survival [ Time Frame: Start of treatment to death ]

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2. Secondary:

Progression Free Survival [ Time Frame: Start of treatment to disease progression or death ]

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3. Secondary:

Number of Participants Who Had a Disease Response to Treatment [ Time Frame: Every 42 days from start of treatment until disease response ]

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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
The study was stopped following a pre-planned interim analysis because the goal for this study to continue was not met, based on 100 events, a reduction in the hazard ratio for progression-free survival by > 23% with a one-sided p-value < 0.1

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:	NCT00473889 History of Changes
Other Study ID Numbers:	2006_539, MK0683-056
Study First Received:	May 14, 2007
Results First Received:	September 3, 2009
Last Updated:	April 20, 2010
Health Authority:	United States: Food and Drug Administration