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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Lung Cancer; Mesothelioma

Treatments: Drug: Vorinostat; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00128102

0683-014

CTRI/2009/091/000146 (Registry Identifier)

2005_010 (Other Identifier)

MK-0683-014 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

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.

Enrollment: 661 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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661 participants in 2 patient groups, including a placebo group

Vorinostat

Experimental group

Description:

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.

Treatment:

Drug: Vorinostat

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo