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

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

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

Study Overview

• Status: Completed
• Conditions: Advanced Cancer Relapsed; Advanced Cancer Refractory
• Intervention / Treatment: Drug: vorinostat; Drug: Comparator: placebo (unspecified)

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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: Zolinza®; MK0683; 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: Zolinza®; MK0683; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in QTcF at 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.	Baseline and 0.5 hours
Change From Baseline in QTcF at 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.	Baseline and 1 hour
Change From Baseline in QTcF at 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.	Baseline and 2 hours
Change From Baseline in QTcF at 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.	Baseline and 3 hours
Change From Baseline in QTcF at 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.	Baseline and 4 hours
Change From Baseline in QTcF at 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.	Baseline and 8 hours
Change From Baseline in QTcF at 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.	Baseline and 12 hours
Change From Baseline in QTcF at 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.	Baseline and 24 hours

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: February 29, 2008
• First Submitted That Met QC Criteria: February 29, 2008
• First Posted (Estimate): March 11, 2008

Study Record Updates

• Last Update Posted (Estimate): July 30, 2015
• Last Update Submitted That Met QC Criteria: July 8, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Vorinostat
• Other Study ID Numbers: 0683-070; MK0683-070; 2008_515