Suberoylanilide Hydroxamic Acid (Vorinostat, MK-0683) Versus Placebo in Advanced Malignant Pleural Mesothelioma (MK-0683-014)
Condition: Mesothelioma; Lung Cancer
MeSH terms: Mesothelioma; Mesothelioma, Malignant
Intervention: Vorinostat; Placebo
Intervention description: Vorinostat 100 mg oral capsules; Vorinostat-matching placebo oral capsules
Intervention MeSH terms: Vorinostat
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 661.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced malignant pleural mesothelioma

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria :

          -  18 years or older with confirmed diagnosis of malignant pleural mesothelioma

          -  In countries where pemetrexed is 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

          -  Received no more than 2 prior systemic therapy regimens

          -  Karnofsky performance scale status of ≥70

          -  Has 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

          -  Randomized to the placebo arm and: 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)

          -  Randomized to vorinostat and 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:

          -  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.

          -  Has 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

          -  Has uncontrolled brain metastases

          -  Has a known human immunodeficiency virus (HIV) infection or HIV-related malignancy

          -  Is pregnant or breast feeding

          -  Has a history of gastrointestinal surgery or other procedures that might interfere
             with the absorption or swallowing of the study drug