A Crossover Study to Assess the Effects of Vorinostat (MK0683, SAHA) in Patients With Advanced Cancer (0683-070)(COMPLETED)

• ClinicalTrials.gov Identifier: NCT00632931
• Recruitment Status: Completed
• First Posted: March 11, 2008
• Results First Posted: February 15, 2010
• Last Update Posted: July 30, 2015
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

A 2-period, crossover study to assess the effects of MK0683 (vorinostat) on the QTc interval in patients with relapsed or refractory advanced cancer.

Condition or disease	Intervention/treatment	Phase
Advanced Cancer Relapsed; Advanced Cancer Refractory	Drug: vorinostat; Drug: Comparator: placebo (unspecified)	Phase 1

Detailed Description:

Merck Duration of Treatment : vorinostat; treatment will continue until disease progression or intolerable toxicity is reached

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Randomized, Partially-Blind, Placebo-Controlled, 2-Period Crossover Study to Assess the Effects of a Single Dose of Vorinostat on the QTc Interval in Patients With Advanced Cancer
• Study Start Date: July 2007
• Actual Primary Completion Date: May 2008
• Actual Study Completion Date: April 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: A; Arm A: Drug/Placebo	Drug: vorinostat; A 2-part, crossover study. Part 1: Arm A: Single dose of vorinostat 800 mg capsules (Period 1) crossing over to Single dose of vorinostat Placebo capsules (Period 2) Arm B: Single dose of vorinostat Placebo capsules (Period 1) crossing over to Single dose of vorinostat 800 mg capsules (Period 2). Part 2: All patients will receive 400 mg vorinostat capsules once daily. Treatment will continue until disease progression or intolerable toxicity.; Other Names: MK0683; Zolinza®; Drug: Comparator: placebo (unspecified); A 2-part, crossover study. Part 1: Arm A: Single dose of vorinostat Placebo capsules (Period 2) Arm B: Single dose of vorinostat Placebo capsules (Period 1).
Experimental: B; Arm B: Placebo/Drug	Drug: vorinostat; A 2-part, crossover study. Part 1: Arm A: Single dose of vorinostat 800 mg capsules (Period 1) crossing over to Single dose of vorinostat Placebo capsules (Period 2) Arm B: Single dose of vorinostat Placebo capsules (Period 1) crossing over to Single dose of vorinostat 800 mg capsules (Period 2). Part 2: All patients will receive 400 mg vorinostat capsules once daily. Treatment will continue until disease progression or intolerable toxicity.; Other Names: MK0683; Zolinza®; Drug: Comparator: placebo (unspecified); A 2-part, crossover study. Part 1: Arm A: Single dose of vorinostat Placebo capsules (Period 2) Arm B: Single dose of vorinostat Placebo capsules (Period 1).

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in QTcF at 0.5 Hours [ Time Frame: Baseline and 0.5 hours ]
   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.
2. Change From Baseline in QTcF at 1 Hour [ Time Frame: Baseline and 1 hour ]
   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.
3. Change From Baseline in QTcF at 2 Hours [ Time Frame: Baseline and 2 hours ]
   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.
4. Change From Baseline in QTcF at 3 Hours [ Time Frame: Baseline and 3 hours ]
   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.
5. Change From Baseline in QTcF at 4 Hours [ Time Frame: Baseline and 4 hours ]
   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.
6. Change From Baseline in QTcF at 8 Hours [ Time Frame: Baseline and 8 hours ]
   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.
7. Change From Baseline in QTcF at 12 Hours [ Time Frame: Baseline and 12 hours ]
   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.
8. Change From Baseline in QTcF at 24 Hours [ Time Frame: Baseline and 24 hours ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patient has a histologically-confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy or for which standard therapy does not exist
• Patient has life expectancy of greater than 3 months
• Patient is able to swallow capsules

Exclusion Criteria:

• Patient has had chemotherapy, radiotherapy or biological therapy 2 weeks prior to taking study drug
• Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent
• Patient has active CNS metastases and/or carcinomatous meningitis
• Patient has primary central nervous system tumor
• Patient has a history of drug or alcohol abuse
• Patient has Hepatitis B or C
• Patient is HIV positive
• Patient has active infection or has received intravenous antibiotics, antiviral or antifungal agents 2 weeks before taking study drug

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Monitor; Merck Sharp & Dohme Corp.

More Information

Publications of Results:

Munster PN, Rubin EH, Van Belle S, Friedman E, Patterson JK, Van Dyck K, Li X, Comisar W, Chodakewitz JA, Wagner JA, Iwamoto M. A single supratherapeutic dose of vorinostat does not prolong the QTc interval in patients with advanced cancer. Clin Cancer Res. 2009 Nov 15;15(22):7077-84. doi: 10.1158/1078-0432.CCR-09-1214. Epub 2009 Nov 3.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT00632931
• Other Study ID Numbers: 0683-070; MK0683-070; 2008_515
• First Posted: March 11, 2008
• Results First Posted: February 15, 2010
• Last Update Posted: July 30, 2015
• Last Verified: July 2015

Additional relevant MeSH terms:

Neoplasms; Vorinostat; Antineoplastic Agents; Histone Deacetylase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action