Suberoylanilide Hydroxamic Acid (Vorinostat, MK-0683) Versus Placebo in Advanced Malignant Pleural Mesothelioma (0683-014 AM5, EXT1) - Full Text View

Sponsor:	Merck
Information provided by:	Merck
ClinicalTrials.gov Identifier:	NCT00128102

Purpose

This is a study to determine the safety, tolerability, and anti-tumor effectiveness of an oral investigational drug, suberoylanilide hydroxamic acid, in the treatment of advanced malignant pleural mesothelioma.

Condition	Intervention	Phase
Mesothelioma Lung Cancer	Drug: vorinostat Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Oral Suberoylanilide Hydroxamic Acid (Vorinostat, MK-0683) in Patients With Advanced Malignant Pleural Mesothelioma Previously Treated With Systemic Chemotherapy

Resource links provided by NLM:

Genetics Home Reference related topics: hereditary multiple exostoses

MedlinePlus related topics: Cancer Lung Cancer Mesothelioma

Drug Information available for: Suberoylanilide hydroxamic acid

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Overall survival [ Time Frame: From Day 1 of study treatment to the time of death from any cause ] [ Designated as safety issue: No ]
Number of participants with adverse events characterized as Grade 3/4 according to the National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) [ Time Frame: From the day of enrollment in the study until 30 days after the last dose of study drug ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Progression-free survival [ Time Frame: From Day 1 of study treatment until disease progression or death from any cause ] [ Designated as safety issue: No ]
Progression-free survival is defined as the time from randomization to the time when the meso-modified response evaluation criteria in solid tumors (RECIST) for mesothelioma are first met for disease progression or when death from any cause occurs
Objective response rate [ Time Frame: Tumor assessments will be performed at baseline and every 42 days from the after the first dose during the first year of treatment and every 84-90 days thereafter ] [ Designated as safety issue: No ]
Overall objective response rate is defined as the ratio of participants with responses over the total number of patients in the analysis population. Overall objective response consists of a complete response (CR) or partial response (PR) based on the meso-modified response evaluation criteria in solid tumors (RECIST) for mesothelioma occurring anytime during the study
Percent change from baseline in dyspnea score of the Lung Cancer Symptom Scale modified for mesothelioma (LCSS-Meso) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
Percent change from baseline in forced vital capacity (FVC) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

Estimated Enrollment:	660
Study Start Date:	June 2005
Estimated Study Completion Date:	November 2012
Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Vorinostat Vorinostat	Drug: vorinostat Vorinostat three 100 mg capsules twice daily for 3 consecutive days of treatment followed by 4 days of rest repeated weekly, in 21-day cycles. Treatment will continue until disease progression or unacceptable toxicity. Other Name: Zolinza, MK-0683
Placebo Comparator: Placebo Placebo	Drug: Placebo Placebo capsules twice daily for 3 consecutive days of treatment followed by 4 days of rest repeated weekly, in 21-day cycles. Treatment will continue until disease progression or unacceptable toxicity.

Detailed Description:

Treatment Extension Phase: Participants in this study will be eligible to enroll in an open-label treatment extension phase if they: a) were originally randomized to the vorinostat arm and have not experienced disease progression; b) were randomized to the placebo arm and meet the "Extension Phase Inclusion Criteria for Participants in the Placebo Arm" below; or c) were originally randomized to the vorinostat arm and discontinued study therapy for reasons other than progression and the investigator believes that it is in the participant's best interest to resume vorinostat treatment.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria :

Participant must be 18 years or older with confirmed diagnosis of malignant pleural mesothelioma
In countries where pemetrexed an approved mesothelioma treatment, the participant's disease has progressed or relapsed following treatment with at least one prior chemotherapy regimen with pemetrexed and either cisplatin or carboplatin OR In countries where pemetrexed is not approved for mesothelioma, the participant's disease has progressed or relapsed following treatment with at least one prior chemotherapy regimen OR Pemetrexed is not the preferred therapy for the participant and the participant's disease has progressed or relapsed following treatment with at least one prior chemotherapy regimen
Participants must have received no more than 2 prior systemic therapy regimens
Participant has a Karnofsky performance scale status of ≥70
Participant must have adequate bone marrow, liver, and kidney function and adequate coagulation (per prespecified laboratory values)

Extension Phase Inclusion Criteria:

Participants who are receiving treatment with vorinostat and have not experienced progression of mesothelioma
Participants who were randomized to the placebo arm and are: 1) have a Karnofsky performance scale status of ≥70; and 2) have adequate bone marrow, liver, and kidney function and adequate coagulation (per prespecified laboratory values)
Participants assigned to vorinostat who have discontinued study therapy for reasons other than progression of mesothelioma, if the investigator is of the opinion that the potential benefit outweighs potential risks associated with using vorinostat

Exclusion Criteria :

Participant has been treated with a Histone deacetylase [HDAC] inhibitor
Participant has an active infection for which they received treatment with intravenous antibiotic, antiviral, or antifungal medications within 2 weeks of the start of study drug.
Participants with a "currently active" second malignancy. A malignancy is not considered "currently active" if participants have completed therapy for the second malignancy and are disease free from prior malignancies for >5 years
Participant has uncontrolled brain metastases
Participant has a known human immunodeficiency virus (HIV) infection or HIV-related malignancy
Participant is pregnant or breast feeding
Participant has a history of gastrointestinal surgery or other procedures that might interfere with the absorption or swallowing of the study drug
Participants taking part in the pre-dose spot and post-first dose 24-hour urine collections must exclude medications containing acetominophen or paracetamol for one week prior to the start of vorinostat therapy and during the entire period of urine collection
Participants taking part in the pre-dose spot and post-first dose 24-hour urine collections may not be using hemodialysis or peritoneal dialysis

Contacts and Locations

No Contacts or Locations Provided

More Information

No publications provided

Responsible Party:	Vice President of Late Stage Development, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00128102 History of Changes
Obsolete Identifiers:	NCT00265577, NCT00290784
Other Study ID Numbers:	MK-0683-014, 2005_010
Study First Received:	August 5, 2005
Last Updated:	August 9, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Merck:

Advanced malignant pleural mesothelioma

Additional relevant MeSH terms:

Lung Neoplasms
Mesothelioma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Adenoma
Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type
Neoplasms, Mesothelial
Vorinostat
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012