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

NCT ID: NCT00128102

Last Updated: 2020-10-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 661 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-30
• Study Completion Date: 2011-11-21

Brief 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.

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.

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.

Conditions

Mesothelioma; Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Vorinostat

Intervention Type: DRUG

Vorinostat 100 mg oral capsules

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Vorinostat-matching placebo oral capsules

Interventions

Vorinostat

Vorinostat 100 mg oral capsules

Intervention Type: DRUG

Placebo

Vorinostat-matching placebo oral capsules

Intervention Type: DRUG

Other Intervention Names

MK-0683; Zolinza

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)

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Krug LM, Kindler HL, Calvert H, Manegold C, Tsao AS, Fennell D, Ohman R, Plummer R, Eberhardt WE, Fukuoka K, Gaafar RM, Lafitte JJ, Hillerdal G, Chu Q, Buikhuisen WA, Lubiniecki GM, Sun X, Smith M, Baas P. Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Oncol. 2015 Apr;16(4):447-56. doi: 10.1016/S1470-2045(15)70056-2. Epub 2015 Mar 20.

Reference Type: RESULT

PMID: 25800891 (View on PubMed)

Other Identifiers

2005_010

Identifier Type: OTHER

Identifier Source: secondary_id

CTRI/2009/091/000146

Identifier Type: REGISTRY

Identifier Source: secondary_id

MK-0683-014

Identifier Type: OTHER

Identifier Source: secondary_id

0683-014

Identifier Type: -

Identifier Source: org_study_id

NCT00265577

Identifier Type: -

Identifier Source: nct_alias

NCT00290784

Identifier Type: -

Identifier Source: nct_alias