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

NCT00128102 | Completed Phase 3 Results DMC

• 4 other identifiers: 0683-0142005_010CTRI/2009/091/000146MK-0683-014
• Study Type: interventional
• Target: 661
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Mesothelioma; Lung Cancer

Keywords

Advanced malignant pleural mesothelioma

Outcome Measures

Primary Outcomes (4)

• Overall Survival (OS)

  OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of final analysis were censored at the date of the last follow up. The final analysis for OS was planned and performed at the time of the protocol pre-specified final statistical analysis with a data cut-off of 15-July-2011. OS analysis is reported here for all randomized participants.

  Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011)

• 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)

  An AE was defined as any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with the use of the Sponsor's product whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the Sponsor's product is also an AE. Reporting of AEs per NCI CTCAE is based on 5 grades of severity; Grade 1 (mild; no treatment needed), Grade 2 (moderate; minimal treatment needed), Grade 3 (severe, not life threatening; hospitalization needed), Grade 4 (life threatening; urgent treatment needed) and Grade 5 (death).The final analysis for Grade 3 or 4 AEs was planned and performed at the time of the protocol pre-specified final statistical analysis with a data cut-off of 15-July-2011. Per protocol number of participants who experienced Grade 3/4 AEs per NCI CTCAE is reported here for all randomized participants who received ≥1 dose of study treatment.

  Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011)

• Number of Participants Who Experienced an AE

  An AE was defined as any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with the use of the Sponsor's product whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the Sponsor's product is also an AE. The final analysis for participants who experienced an AE was planned and performed at the time of the protocol pre-specified final statistical analysis with a data cut-off of 15-July-2011. Per protocol number of participants who experienced an AE is reported here for all randomized participants who received ≥1 dose of study treatment.

  Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011)

• Number of Participants Who Discontinued Study Treatment Due to an AE

  An AE was defined as any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with the use of the Sponsor's product whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the Sponsor's product is also an AE. The final analysis for participants who discontinued study treatment due to an AE was planned and performed at the time of the protocol pre-specified final statistical analysis with a data cut-off of 15-July-2011. Per protocol number of participants who discontinued study treatment due to an AE is reported here for all randomized participants who received ≥1 dose of study treatment. As specified by the protocol, participants who discontinued study treatment due to an AE remained on study until investigator notification to discontinue.

  Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011)

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011)

• Objective Response Rate (ORR)

  Up to ~72 months (through pre-specified final statistical analysis cut-off date of 15-July-2011)

• Percent Change From Baseline in Lung Cancer Symptom Scale, Modified for Mesothelioma (LCSS-Meso) Dyspnea Score at Week 12

  Baseline, Week 12

• Percentage of Participants With ≥50% Change Together With a >10 mm Change From Baseline in the LCSS-Meso Dyspnea Score at Week 12

  Baseline, Week 12

• Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 12

  Baseline, Week 12

Study Arms (2)

Vorinostat

EXPERIMENTAL

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.

Drug: Vorinostat

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Vorinostat DRUG

Vorinostat 100 mg oral capsules

Also known as: MK-0683, Zolinza

Vorinostat

Placebo DRUG

Vorinostat-matching placebo oral capsules

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 25800891 RESULT

MeSH Terms

Conditions

Mesothelioma; Lung Neoplasms

Interventions

Vorinostat

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2005
• First Posted: August 9, 2005
• Study Start: June 30, 2005
• Primary Completion: July 15, 2011
• Study Completion: November 21, 2011
• Last Updated: October 26, 2020
• Results First Posted: October 26, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share