A Phase II Study of Bevacizumab and Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma
The purpose of this study is to determine whether the combination of bevacizumab and bortezomib have increased efficacy in the treatment of relapsed/ refractory multiple myeloma.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Bevacizumab and Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma|
- Time to Tumor Progression (TTP)
- TTP is calculated at the time from randomization to the first documentation of progressive disease based on the myeloma response determination criteria developed by Bladé et al (Appendix F). If disease progression is based on increasing monoclonal parap
- Overall Survival (OS)
- Overall survival is calculated at the time of the screening evaluation to death from any cause.
|Study Start Date:||April 2007|
|Study Completion Date:||February 2009|
Rationale: With the identification of thalidomide as an active agent in Multiple Myeloma, the role of angiogenesis in its pathogenesis has become a subject of much investigation. Micro vessel density (neovascularization) is inversely related to prognosis in Multiple Myeloma. Response to thalidomide was felt to correlate with a decline in microvessel density (Singhal et al NEJM). While the mechanism of neovascularization is yet to be fully elucidated, a number of models have shown VEGF to play a central role.
Thalidomide has been shown to synergize with a number of agents used to treat MM, including bortezomib. (Wang et al ASH 2005) This would justify the use of other therapeutics with known antiangiogenic activity in conjunction with established antimyeloma therapies.
Bortezomib, which has the precedence of known synergy with Thalidomide and has an extremely well established optimal dose, schedule, response rate, event free survival, and overall survival would make it an excellent candidate for combination therapy with other established antiangiogenic compounds.
There have been several reports of the role of VEGF in multiple myeloma. It has been shown that multiple myeloma cells secreteVEGF, which further promotes production of IL-6 in BMSCs, as well as migration and proliferation of the tumor cells. Thus VEGF is both an autocrine growth factor and trigger of IL-6-mediated paracrine multiple myeloma cell growth. Recent reports have highlighted the major role of VEGF in multiple myeloma pathogenesis, demonstrating the VEGF also increases microvessel density in the bone marrow. VEGF also inhibits dendritic cells. Taken together, these preclinical reports make strong suggestion for the promise of VEGF targeted agents in multiple myeloma (Le Gouill et al 2004).
|United States, New Jersey|
|The Cancer Center at Hackensack University Medical Center|
|Hackensack, New Jersey, United States, 07601|
|Principal Investigator:||David S Siegel, MD, PhD||The Cancer Center at Hackensack University Medical Center|