Temsirolimus and Pazopanib in Patients With Advanced Solid Tumors
The purpose of this study is to test the safety of temsirolimus and pazopanib at different doses. Patients who have an advanced cancer that is not felt to benefit from standard treatment or are no longer responding to other treatment will be asked to take part in this study. The study hypothesis is that temsirolimus and pazopanib can be administered safely in combination and that combined targeting of the mammalian target of rapamycin (mTOR) and vascular endothelial growth factor receptor (VEGFR) signaling pathways will be effective in treating patients with advanced solid tumors.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of the Combination of Temsirolimus (CCI-779) and Pazopanib (GW786034) in Patients With Advanced Solid Tumors|
- Feasibility and safety of temsirolimus and pazopanib when given in combination to patients with advanced solid tumors. [ Time Frame: Every 4 weeks (Cycle) ] [ Designated as safety issue: Yes ]
- Determine the maximum tolerated dose (MTD) of temsirolimus and pazopanib when given in combination to patients with advanced solid tumors and to recommend a phase II dose for the combination. [ Time Frame: Every 4 weeks (Cycle) ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2010|
|Study Completion Date:||February 2012|
|Primary Completion Date:||February 2012 (Final data collection date for primary outcome measure)|
|Experimental: Temsirolimus and Pazopanib||
Drug: Temsirolimus, Pazopanib
Patients will be treated on an outpatient basis with both temsirolimus and pazopanib. All patients will receive temsirolimus intravenously (IV) weekly days 1, 8, 15, and 22. Patients will receive oral pazopanib on a daily basis starting day 1. Treatment will be administered on 28 day cycles. Patients will be in this study for a minimum of 8 weeks or 2 cycles.
Despite encouraging clinical activity reported with single-agent VEGF inhibitors, mTOR inhibitors, and other novel agents, patients rarely achieve complete disease response and ultimately undergo disease progression. The limited efficacy of single-target inhibition may be due to numerous, overlapping signaling pathways involved in Renal Cell Carcinoma proliferation and growth. A strategy of multi-target "vertical inhibition" of the overlapping aberrant VEGF and mTOR pathways by combination therapy may translate to enhanced efficacy over each single agent alone. We hypothesize that temsirolimus and pazopanib can be administered safely in combination and that combined targeting of the mTOR and VEGFR signaling pathways will be effective in treating patients with advanced solid tumors.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01072890
|United States, California|
|University of California Davis Cancer Center|
|Sacramento, California, United States, 95817|
|Principal Investigator:||Primo N Lara, MD||University of California, Davis|