Phase 3
N=661
Suberoylanilide Hydroxamic Acid (Vorinostat, MK-0683) Versus Placebo in Advanced Malignant Pleural Mesothelioma (MK-0683-014)
Mesothelioma · Lung Cancer
Bottom Line
View on ClinicalTrials.gov: NCT00128102 ↗Enrolled (actual)
661
Serious AEs
40.1%
Results posted
Oct 2020
Primary outcome: Primary: Overall Survival (OS) — 30.7; 27.1 Weeks — p=0.858
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Vorinostat (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Jul 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Survival (OS) |
30.7; 27.1 | 0.858 |
| PRIMARY 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) |
165; 146 | — |
| PRIMARY Number of Participants Who Experienced an AE |
327; 311 | — |
| PRIMARY Number of Participants Who Discontinued Study Treatment Due to an AE |
60; 49 | — |
| SECONDARY Progression Free Survival (PFS) |
6.3; 6.1 | <0.001 sig |
| SECONDARY Objective Response Rate (ORR) |
0.63; 0.31 | 0.621 |
| SECONDARY Percent Change From Baseline in Lung Cancer Symptom Scale, Modified for Mesothelioma (LCSS-Meso) Dyspnea Score at Week 12 |
141.8; 174.7 | 0.259 |
| SECONDARY Percentage of Participants With ≥50% Change Together With a >10 mm Change From Baseline in the LCSS-Meso Dyspnea Score at Week 12 |
15.05; 16.39 | 0.736 |
| SECONDARY Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 12 |
-6.0; -5.6 | 0.979 |
| SECONDARY Percentage of Participants With ≥10% Change From Baseline in FVC at Week 12 |
24.76; 21.63 | 0.488 |
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
Data sourced from ClinicalTrials.gov (NCT00128102). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.