Tracking Information
Start Date ICMJE | December 2008 |
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Estimated Primary Completion Date | September 2011 (final data collection date for primary outcome measure) |
Current Primary Outcome Measures ICMJE (submitted: November 5, 2009) | Determine the PFS (progression free survival) [ Time Frame: every 21 days ] [ Designated as safety issue: No ] |
Original Primary Outcome Measures ICMJE (submitted: October 15, 2008) | Determine the TTP (time-to-progression) in patients with multiple myeloma, treated with bortezomib and vorinostat compared to patients treated with bortezomib and placebo [ Time Frame: 33 months ] [ Designated as safety issue: No ] |
Change History | Complete list of historical versions of study NCT00773747 on ClinicalTrials.gov Archive Site |
Current Secondary Outcome Measures ICMJE (submitted: November 5, 2009) |
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Original Secondary Outcome Measures ICMJE (submitted: October 15, 2008) | Assess the tolerability of vorinostat administered in combination with bortezomib. [ Time Frame: 33 months ] [ Designated as safety issue: Yes ] |
Descriptive Information
Brief Title ICMJE | Study of Vorinostat (MK0683) an HDAC Inhibitor, or Placebo in Combination With Bortezomib in Patients With Multiple Myeloma |
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Official Title ICMJE | An International, Multicenter, Randomized, Double-Blind Study of Vorinostat (MK0683) or Placebo in Combination With Bortezomib in Patients With Multiple Myeloma |
Brief Summary | Study of bortezomib administered in combination with vorinostat or placebo in patients with relapsed or refractory multiple myeloma. Histone deacetylases (HDAC) facilitate gene transcription by modulating the uncoiling of chromatin. HDAC function is dysregulated in hematologic and solid malignancies, and this dysregulation may result in over-expression of oncogenes. Thus, inhibition of HDACs may result in anti-cancer effects. HDAC inhibitors, like vorinostat, represent a new class of antitumor agents that have the ability to induce antiproliferative effects including cyto-differentiation, cell cycle growth arrest or apoptosis in various cancer cell lines. Several studies have investigated the in vitro antimyeloma activity of vorinostat in combination with bortezomib and have demonstrated that vorinostat may act synergistically with bortezomib to modulate tumor cell growth. Mitsiades et al have shown that vorinostat enhances the sensitivity of bortezomib. Pei et al found that exposure of human multiple myeloma cell lines & patient-derived multiple myeloma cells to bortezomib and vorinostat resulted in synergistic interactions as a result of: (1) Interruption of NF-kB & related signaling pathways (JNK, XIAP, Mcl-1, etc.) (2) Inhibition of Hsp90 (3) Induction of ER stress signal and (4) acetylation of Dynein/ disruption of aggresome function/formation, salvage for ubiquitinated proteins. In addition a marked increase in mitochondrial injury, caspase activation, and apoptosis was also observed. Bortezomib is indicated for the treatment of patients with multiple myeloma. Two Phase I dose-ranging studies of a regimen combining vorinostat and bortezomib among patients with relapsed as well as end-stage, refractory multiple myeloma have been conducted. These studies enrolled a total of 57 patients. In these studies, administration of vorinostat with standard doses of bortezomib resulted in responses in 20/45 (44%) evaluable patients (Weber et al 2007, Badros et al 2007). The purpose of the present study is to definitively evaluate the clinical activity of vorinostat in combination with bortezomib in patients with multiple myeloma |
Detailed Description | |
Study Phase | Phase III |
Study Type ICMJE | Interventional |
Study Design ICMJE | Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Single Group Assignment, Efficacy Study |
Condition ICMJE | Multiple Myeloma |
Intervention ICMJE |
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Study Arms / Comparison Groups |
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Recruitment Information
Estimated Enrollment ICMJE | 742 | ||||
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Estimated Completion Date | October 2011 | ||||
Estimated Primary Completion Date | September 2011 (final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria: Patient is 18 years of age or older
Exclusion Criteria:
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Gender | Both | ||||
Ages | 18 Years and older | ||||
Accepts Healthy Volunteers | No | ||||
Contacts ICMJE |
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Location Countries ICMJE | United States, Australia, Belgium, Bulgaria, Canada, Czech Republic, Germany, Greece, Hungary, India, Italy, Korea, Republic of, Malaysia, Mexico, New Zealand, Poland, Portugal, Russian Federation, South Africa, Spain, Taiwan, United Kingdom |
Administrative Information
NCT ID ICMJE | NCT00773747 | ||||
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Responsible Party | Executive Vice President, Clinical and Quantitative Sciences, Merck & Co., Inc. | ||||
Study ID Numbers ICMJE | 2008_525, MK0683-088 | ||||
Study Sponsor ICMJE | Merck | ||||
Collaborators ICMJE | |||||
Investigators ICMJE |
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Information Provided By | Merck |