A Study of Oral Suberoylanilide Hydroxamic Acid (Vorinostat) in Patients With Solid Tumors (0683-048)

MK0683 Phase1 Clinical Study - Solid Tumor -

This is a clinical study to evaluate the safety and pharmacokinetics of an overseas determined maximum tolerated dose (MTD) of MK-0683 (vorinostat) in a Japanese patient population with solid tumors.

Study Overview

• Status: Completed
• Conditions: Tumors
• Intervention / Treatment: Drug: Vorinostat; Drug: Vorinostat

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with histologically or cytologically diagnosed solid tumor in whom no standard therapy is available or the malignancy is refractory to standard therapy

Exclusion Criteria:

• Patients with history of immunotherapy, radiotherapy, surgery, or chemotherapy during the previous 4 weeks
• Any uncontrolled concomitant illness
• Pregnant or breast-feeding
• Serious drug or food allergy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vorinostat 600 mg; 600 mg daily (300 mg twice daily [b.i.d.]) for 3 consecutive days followed by 4 days of rest.	Drug: Vorinostat; 600 mg daily (300 mg twice daily [b.i.d.]) for 3 consecutive days followed by 4 days of rest.; Other Names: MK-0683; Suberoylanilide Hydroxamic Acid (SAHA); Drug: Vorinostat; 400 mg once daily (400 mg q.d.) continuous daily dosing for 21 days.; Other Names: MK-0683; Suberoylanilide Hydroxamic Acid (SAHA)
Experimental: Vorinostat 400 mg; 400 mg once daily (400 mg q.d.) continuous daily dosing for 21 days.	Drug: Vorinostat; 600 mg daily (300 mg twice daily [b.i.d.]) for 3 consecutive days followed by 4 days of rest.; Other Names: MK-0683; Suberoylanilide Hydroxamic Acid (SAHA); Drug: Vorinostat; 400 mg once daily (400 mg q.d.) continuous daily dosing for 21 days.; Other Names: MK-0683; Suberoylanilide Hydroxamic Acid (SAHA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Dose Limiting Toxicity (DLT)	Dose Limiting Toxicity = Drug-related side effects that are serious enough to prevent an increase in dose or level of that treatment	21 Days (first cycle)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve (AUC(0-infinity)) at Day 1 (600 mg and 400 mg)	Area Under Curve (AUC(0-infinity))=Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (o- ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). At 600 mg, t=12 hours and at 400 mg, t=24 hours.	Day 1 (600 mg and 400 mg)
Area Under the Curve (AUC(0-infinity)) at Day 3 (600 mg)	Area Under Curve (AUC(0-infinity))=Area under the plasma concentration versus time curve (AUC) from time zero to 24 ｈours. It is obtained from AUC (0 - 12) plus AUC (12 - ∞)	Day 3 (600 mg)
Area Under the Curve (AUC(0-infinity) at Day 21 (400 mg)	Area Under Curve (AUC(0-infinity))=Area under the plasma concentration versus time curve (AUC) from time zero to 24 ｈours. It is obtained from AUC (0 - 24) plus AUC (24 - ∞)	Day 21 (400 mg)
Maximum Concentration (Cmax) at Day 1 (600 mg and 400 mg)		Day 1 (600 mg and 400 mg)
Maximum Concentration (Cmax) at Day 3 (600 mg)		Day 3 (600 mg)
Maximum Concentration (Cmax) at Day 21 (400 mg)		Day 21 (400 mg)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Doi T, Hamaguchi T, Shirao K, Chin K, Hatake K, Noguchi K, Otsuki T, Mehta A, Ohtsu A. Evaluation of safety, pharmacokinetics, and efficacy of vorinostat, a histone deacetylase inhibitor, in the treatment of gastrointestinal (GI) cancer in a phase I clinical trial. Int J Clin Oncol. 2013 Feb;18(1):87-95. doi: 10.1007/s10147-011-0348-6. Epub 2012 Jan 11.

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: September 7, 2006
• First Submitted That Met QC Criteria: September 7, 2006
• First Posted (Estimate): September 8, 2006

Study Record Updates

• Last Update Posted (Estimate): August 27, 2015
• Last Update Submitted That Met QC Criteria: August 26, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Vorinostat
• Other Study ID Numbers: 0683-048; MK0683-048; 2006_030