Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Rare Diseases

Lung Neoplasms

Mesothelioma

Mesothelioma, Malignant

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Malignant Mesothelioma

Antineoplastic Agents

All Drugs and Chemicals

Vorinostat

Histone Deacetylase Inhibitors

Enzyme Inhibitors

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.

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.

Vorinostat-matching placebo oral capsules

Placebo

Medical Director

The goal of this study is to assess the efficacy and safety of an oral investigational drug suberoylanilide hydroxamic acid (vorinostat, MK-0683) compared to placebo, in the treatment of participants with advanced malignant pleural mesothelioma who have failed at least one prior chemotherapy regimen. The primary hypotheses are the following: (1) vorinostat improves overall survival (OS) compared to placebo (2) vorinostat is generally safe and well tolerated.

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.

As specified by the protocol, based on planned extension phase inclusion criteria and pre-specified primary outcome analyses requirements, the extension phase of this study was not conducted.

Suberoylanilide Hydroxamic Acid (Vorinostat, MK-0683) Versus Placebo in Advanced Malignant Pleural Mesothelioma (MK-0683-014)

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

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of final analysis were censored at the date of the last follow up. The final analysis for OS was planned and performed at the time of the protocol pre-specified final statistical analysis with a data cut-off of 15-July-2011. OS analysis is reported here for all randomized participants.

An AE was defined as any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with the use of the Sponsor's product whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the Sponsor's product is also an AE. Reporting of AEs per NCI CTCAE is based on 5 grades of severity; Grade 1 (mild; no treatment needed), Grade 2 (moderate; minimal treatment needed), Grade 3 (severe, not life threatening; hospitalization needed), Grade 4 (life threatening; urgent treatment needed) and Grade 5 (death).The final analysis for Grade 3 or 4 AEs was planned and performed at the time of the protocol pre-specified final statistical analysis with a data cut-off of 15-July-2011. Per protocol number of participants who experienced Grade 3/4 AEs per NCI CTCAE is reported here for all randomized participants who received ≥1 dose of study treatment.

An AE was defined as any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with the use of the Sponsor's product whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the Sponsor's product is also an AE. The final analysis for participants who experienced an AE was planned and performed at the time of the protocol pre-specified final statistical analysis with a data cut-off of 15-July-2011. Per protocol number of participants who experienced an AE is reported here for all randomized participants who received ≥1 dose of study treatment.

An AE was defined as any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with the use of the Sponsor's product whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the Sponsor's product is also an AE. The final analysis for participants who discontinued study treatment due to an AE was planned and performed at the time of the protocol pre-specified final statistical analysis with a data cut-off of 15-July-2011. Per protocol number of participants who discontinued study treatment due to an AE is reported here for all randomized participants who received ≥1 dose of study treatment. As specified by the protocol, participants who discontinued study treatment due to an AE remained on study until investigator notification to discontinue.

PFS was defined as the time from randomization to the first documented progressive disease (PD) per meso-modified-Response Evaluation Criteria in Solid Tumors (Meso-modified RECIST) based on independent radiology review or death due to any cause, whichever occurred first. Meso-modified RECIST was created and validated for disease measurement in pleural mesothelioma. Per meso-modified RECIST, PD was defined as ≥20% increase in the total tumor measurement over the nadir measurement or the appearance of ≥1 new lesions. The final analysis for PFS per Meso-modified RECIST by independent radiology review was planned and performed at the time of the protocol pre-specified final statistical analysis with a data cut-off of 15-July-2011. PFS analysis per Meso-modified RECIST by independent radiology review is reported here for all randomized participants.

ORR was defined as the percentage of participants in the analysis population who had a complete response (CR: disappearance of all target lesions with no evidence of tumor elsewhere) or a partial response (PR: ≥30% reduction in the total tumor measurement) per Meso-modified RECIST based on independent radiology review. Meso-modified RECIST was created and validated for disease measurement in pleural mesothelioma. The final analysis for ORR per Meso-modified RECIST by independent radiology review was planned and performed at the time of the protocol pre-specified final statistical analysis with a data cut-off of 15-July-2011. Per protocol percentage of participants who had a CR or a PR per Meso-modified RECIST by independent radiology review is reported here as the ORR for all randomized participants who had valid baseline data for ORR analysis available.

LCSS-Meso provides participant-reported outcome measures of symptom burden and quality of life. LCSS-Meso includes the disease-related item dyspnea or shortness of breath. The LCSS-Meso item dyspnea is measured on a visual analog scale (VAS) using 100 mm and assigned an individual score based on symptom intensity. Dyspnea VAS score ranges from 0 mm (lowest; no dyspnea) to 100 mm (highest; worst dyspnea). Higher scores indicate dyspnea worsening. Baseline measurement was taken before treatment initiation. Per protocol percent change in the LCSS-Meso dyspnea score from baseline to Week 12 post treatment initiation (percent change calculated: \[Week 12 - Baseline\]/Baseline\*100)\] is reported here for all randomized participants who had a valid baseline and ≥1 post-baseline value for the LCSS-Meso dyspnea score available.

LCSS-Meso provides participant-reported outcome measures of symptom burden and quality of life. LCSS-Meso includes the disease-related item dyspnea or shortness of breath. The LCSS-Meso item dyspnea is measured on a visual analog scale (VAS) using 100 mm and assigned an individual score based on symptom intensity. Dyspnea VAS score ranges from 0 mm (lowest; no dyspnea) to 100 mm (highest; worst dyspnea). Higher scores indicate dyspnea worsening. Baseline measurement was taken before treatment initiation. Per protocol percentage of participants with ≥50% change (percent change calculated: \[Week 12 - Baseline\]/Baseline\*100) and \>10 mm absolute change in LCSS-Meso dyspnea score from baseline to Week 12 post treatment initiation is reported here for all randomized participants who had a valid baseline and ≥1 post-baseline value for the LCSS-Meso dyspnea score available.

Pulmonary function test was conducted using a spirometer for assessment of FVC. FVC is the volume of air forcibly exhaled from the lungs after taking the deepest breath possible. Baseline measurement was taken before treatment initiation. Per protocol percent change in FVC from baseline to Week 12 post treatment initiation (percent change calculated: \[Week 12 - Baseline\]/Baseline\*100)\] is reported here for all randomized participants who had a valid baseline and ≥1 post-baseline value for FVC available.

Pulmonary function test was conducted using a spirometer for assessment of FVC. FVC is the volume of air forcibly exhaled from the lungs after taking the deepest breath possible. Baseline measurement was taken before treatment initiation. Per protocol percentage of participants with ≥10% change (percent change calculated: \[Week 12 - Baseline\]/Baseline\*100) in FVC from baseline to Week 12 post treatment initiation is reported here for all randomized participants who had a valid baseline and ≥1 post-baseline value for FVC.

Merck Sharp & Dohme LLC

All-Cause Mortality table includes all randomized participants. Serious AEs and other AEs tables include all randomized participants who got ≥1 dose of study drug. Per protocol disease progression of cancer under study was not considered an AE unless it resulted in hospitalization or death. Thus Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.

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 continued until disease progression or unacceptable toxicity.

Placebo capsules twice daily for 3 consecutive days of treatment followed by 4 days of rest repeated weekly, in 21-day cycles. Treatment continued until disease progression or unacceptable toxicity.

Total

Age, Continuous

Sex: Female, Male

Senior Vice President, Global Clinical Development

All participants randomized to a study arm.

Overall Survival (OS)

All participants randomized to a study arm who received ≥1 dose of study treatment.

Number of Participants Who Experienced Adverse Events (AEs) Characterized as Grade 3 or Grade 4 According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)

Number of Participants Who Experienced an AE

Number of Participants Who Discontinued Study Treatment Due to an AE

Progression Free Survival (PFS)

All participants randomized to a study arm who had valid baseline data for ORR analysis available.

Objective Response Rate (ORR)

All participants randomized to a study arm who had a valid baseline and ≥1 post-baseline value for the LCSS-Meso dyspnea score available.

Percent Change From Baseline in Lung Cancer Symptom Scale, Modified for Mesothelioma (LCSS-Meso) Dyspnea Score at Week 12

Percentage of Participants With ≥50% Change Together With a >10 mm Change From Baseline in the LCSS-Meso Dyspnea Score at Week 12

All participants randomized to a study arm who had a valid baseline and ≥1 post-baseline value for FVC available.

Spots Global Cancer Trial Database for Suberoylanilide Hydroxamic Acid (Vorinostat, MK-0683) Versus Placebo in Advanced Malignant Pleural Mesothelioma (MK-0683-014)

Trial Identification

Conditions

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Study Description

Keywords

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Contact Details

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