Clinical trial NCT00128102: Suberoylanilide Hydroxamic Acid (Vorinostat, MK-0683) Versus Placebo in Advanced Malignant Pleural Mesothelioma (MK-0683-014)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Mesothelioma
Lung Cancer
Keywords: Advanced malignant pleural mesothelioma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2005-08-09
Enrollment: 661
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011)
measure: 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)
timeFrame: Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011)
measure: Number of Participants Who Experienced an AE
timeFrame: Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011)
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011)
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011)
measure: Objective Response Rate (ORR)
timeFrame: Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011)
measure: Percent Change From Baseline in Lung Cancer Symptom Scale, Modified for Mesothelioma (LCSS-Meso) Dyspnea Score at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants With ≥50% Change Together With a >10 mm Change From Baseline in the LCSS-Meso Dyspnea Score at Week 12
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants With ≥10% Change From Baseline in FVC at Week 12
timeFrame: Baseline, Week 12
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.