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

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”

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.

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.

Intervention(s) in this Clinical Trial

• 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.
• 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.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Vorinostat
  • Vorinostat
• Placebo Comparator: Placebo
  • Placebo

Primary Measures

• Overall survival
  • Time Frame: From Day 1 of study treatment to the time of death from any cause
    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
    Safety Issue?: Yes

Secondary Measures

• Progression-free survival
  • Time Frame: From Day 1 of study treatment until disease progression or death from any cause
    Safety Issue?: No
• 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
    Safety Issue?: No
• Percent change from baseline in dyspnea score of the Lung Cancer Symptom Scale modified for mesothelioma (LCSS-Meso)
  • Time Frame: Baseline and Week 12
    Safety Issue?: No
• Percent change from baseline in forced vital capacity (FVC)
  • Time Frame: Baseline and Week 12
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Merck Industry

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00128102

Study ID Number: MK-0683-014

ClinicalTrials.gov Identifier: NCT00128102

Health Authority: United States: Food and Drug Administration