IGF-1 Inhibitor Pasireotide Lar in Combination With the m-TOR Inhibitor Everolimus
Observe the safety/tolerability and effectiveness in terms of response rate and duration of response of the combination pasireotide + everolimus in the treatment of patients with relapsed/refractory multiple melanoma.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of the IGF-1 Inhibitor Pasireotide Lar in Combination With the m-TOR Inhibitor Everolimus in Patients With Relapsed/Refractory Multiple Myeloma|
- Primary objective [ Time Frame: 12 patients enrolled ] [ Designated as safety issue: Yes ]Initially 12 patients will be enrolled. If there are no responses among these patients with the combination pasireotide + everolimus in the treatment the study will be terminated.
- Secondary objective [ Time Frame: 25 to 37 patients enrolled ] [ Designated as safety issue: Yes ]After initial 12 patients enrolled and these patients respond, an additional 25 to 27 patients will be enrolled. We will evaluate efficacy of the combination regimen based primarily on response rate. Progression free-survival and overall survival will also be recorded and analyzed.
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Pasireotide 60 mg day 1 every 28 days
Given as an intramuscular injection on day 1 every 28 days, 60 mg per dose
Other Names:Drug: Everolimus
given as an oral tablet every day on days 1-28, 10 mg per day
Other Name: RAD001
Multiple myeloma (MM) is a B-cell malignancy of plasma cells. It represents the second most common hematological malignancy, with non-Hodgkin's lymphoma being the most common.In this protocol, we propose a regimen consisting of a novel combination of two agents with a promising preclinical activity, i.e., pasireotide (IGF-1 inhibitor) and everolimus (mTOR inhibitor), exploring the efficacy of this therapy in patients with MM. We propose enrollment after failure to the first two lines of FDA-approved agents, even in patients who did not have high-dose chemotherapy and SCT. In fact, overall survival after SCT has been shown to be identical when "early" SCT is compared to "late" SCT, i.e., administered at the time of relapse. This provides an important opportunity to test our novel therapeutic approach, reserving SCT for relapse. The advantage of the this strategy is that similar overall survival outcomes can be achieved with fewer patients undergoing SCT. Both everolimus and pasireotide have the potential of being clinically effective against myeloma. A phase II trial of the mTOR inhibitor temsirolimus, an analogue of everolimus, produced a response rate of 38% in relapsed/refractory multiple myeloma. The IGF-1 inhibitor pasireotide is a promising agent, because IGF has been recently found to be one of the most important growth signal molecule in myeloma cells. The combination of everolimus and pasireotide should have a synergistic antimyeloma effect because preclinical data invitro have shown that combined inhibition of mTOR inhibition and IGF-1 led to a synergistic increase of cell growth inhibition in multiple myeloma cells and might represent a potential new treatment strategy.
|United States, Pennsylvania|
|Penn State Milton S. Hershey Medical Center|
|Hershey, Pennsylvania, United States, 17033|
|Principal Investigator:||Giampaolo Talamo, MD||Milton S. Hershey Medical Center|