Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Suberoylanilide Hydroxamic Acid (Vorinostat, MK-0683) Versus Placebo in Advanced Malignant Pleural Mesothelioma (0683-014 AM5, EXT1)

This study has been completed.
Sponsor:
Information provided by:
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00128102
First received: August 5, 2005
Last updated: April 3, 2012
Last verified: April 2012
  Purpose

This is a study to determine the safety, tolerability, and anti-tumor effectiveness of an oral investigational drug, suberoylanilide hydroxamic acid, in the treatment of advanced malignant pleural mesothelioma.


Condition Intervention Phase
Mesothelioma
Lung Cancer
Drug: vorinostat
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Overall survival [ Time Frame: From Day 1 of study treatment to the time of death from any cause ] [ Designated as safety issue: No ]
  • Number of participants with adverse events characterized as Grade 3/4 according to the National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) [ Time Frame: From the day of enrollment in the study until 30 days after the last dose of study drug ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: From Day 1 of study treatment until disease progression or death from any cause ] [ Designated as safety issue: No ]
    Progression-free survival is defined as the time from randomization to the time when the meso-modified response evaluation criteria in solid tumors (RECIST) for mesothelioma are first met for disease progression or when death from any cause occurs

  • Objective response rate [ Time Frame: Tumor assessments will be performed at baseline and every 42 days from the after the first dose during the first year of treatment and every 84-90 days thereafter ] [ Designated as safety issue: No ]
    Overall objective response rate is defined as the ratio of participants with responses over the total number of patients in the analysis population. Overall objective response consists of a complete response (CR) or partial response (PR) based on the meso-modified response evaluation criteria in solid tumors (RECIST) for mesothelioma occurring anytime during the study

  • Percent change from baseline in dyspnea score of the Lung Cancer Symptom Scale modified for mesothelioma (LCSS-Meso) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent change from baseline in forced vital capacity (FVC) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

Enrollment: 662
Study Start Date: June 2005
Study Completion Date: November 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vorinostat
Vorinostat
Drug: 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.
Other Name: Zolinza, MK-0683
Placebo Comparator: Placebo
Placebo
Drug: 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria :

  • Participant must be 18 years or older with confirmed diagnosis of malignant pleural mesothelioma
  • In countries where pemetrexed 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
  • Participants must have received no more than 2 prior systemic therapy regimens
  • Participant has a Karnofsky performance scale status of ≥70
  • Participant must have 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
  • Participants who were randomized to the placebo arm and are: 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)
  • Participants assigned to vorinostat who 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 :

  • Participant has been treated with a Histone deacetylase [HDAC] inhibitor
  • Participant 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.
  • Participants with 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
  • Participant has uncontrolled brain metastases
  • Participant has a known human immunodeficiency virus (HIV) infection or HIV-related malignancy
  • Participant is pregnant or breast feeding
  • Participant has a history of gastrointestinal surgery or other procedures that might interfere with the absorption or swallowing of the study drug
  • Participants taking part in the pre-dose spot and post-first dose 24-hour urine collections must exclude medications containing acetominophen or paracetamol for one week prior to the start of vorinostat therapy and during the entire period of urine collection
  • Participants taking part in the pre-dose spot and post-first dose 24-hour urine collections may not be using hemodialysis or peritoneal dialysis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Vice President of Late Stage Development, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier: NCT00128102     History of Changes
Obsolete Identifiers: NCT00265577, NCT00290784
Other Study ID Numbers: MK-0683-014, 2005_010
Study First Received: August 5, 2005
Last Updated: April 3, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Advanced malignant pleural mesothelioma

Additional relevant MeSH terms:
Mesothelioma
Neoplasms, Mesothelial
Adenoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Vorinostat
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014