Sorafenib and Temsirolimus in Treating Patients With Metastatic, Recurrent, or Unresectable Melanoma
This phase I trial is studying the side effects and best dose of temsirolimus when given together with sorafenib and to see how well they work in treating patients with metastatic, recurrent, or unresectable melanoma. Sorafenib and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with temsirolimus may kill more tumor cells
Stage III Melanoma
Stage IV Melanoma
Drug: Sorafenib tosylate
|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 BAY 43-9006 (Sorafenib) and CCI-779 (Temsirolimus) in Patients With Metastatic Melanoma|
- Maximum tolerated dose of CCI-779 in combination with BAY43-9006 (Phase I) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]Maximum tolerated dose (MTD) of CCI-779 in combination with BAY43-9006 (Phase I) determined by dose limiting toxicities (DLT) assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I) The MTD is defined as the highest dose studied in which the incidence of DLT is < 33%.
- Progression-free survival [ Time Frame: The duration of time from start of treatment to date of first evidence of progression or the date of last follow-up for patients who do not progress, assessed up to 5 years ] [ Designated as safety issue: No ]Kaplan-Meier life table methods and Cox proportional hazards regression modeling will be utilized to analyze progression-free survival and overall survival.
- Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]Kaplan-Meier life table methods and Cox proportional hazards regression modeling will be utilized to analyze progression-free survival and overall survival.
- Noncompartmental pharmacokinetic parameters of BAY43-9006 and CCI-779 estimated using a validated commercial software [ Time Frame: Week 1 and 3 ] [ Designated as safety issue: No ]Maximum concentration (Cmax) and time to Cmax (tmax) will be the observed values. Area under the plasma concentration-time curve from zero to last observable time (AUClast).
|Study Start Date:||April 2006|
|Study Completion Date:||February 2012|
|Primary Completion Date:||February 2012 (Final data collection date for primary outcome measure)|
Experimental: Temsirolimus + Sorafenib
Weekly Temsirolimus 15 mg intravenous (IV) over 30 minutes on days 1, 8, 15, and 22 and oral sorafenib starting dose 400 mg twice daily on days 1-28.
Drug: Sorafenib tosylate
Given orally twice a day, at either 400 mg or a combination of 400 mg each morning / 200 mg each evening daily.
Other Names:Drug: temsirolimus
Starting dose 15 mg given IV once a week for 4 weeks.
I. To determine the maximum tolerated dose of temsirolimus when administered with sorafenib in patients with metastatic, recurrent, or unresectable melanoma. (Phase I) II. To determine the safety and toxicity of this regimen in these patients. (Phase I)
- To Determine the population pharmacokinetics of this regimen in these patients.
- To correlate tumor and blood biomarkers with clinical outcome in patients treated with this regimen.
OUTLINE: This is a multicenter, phase I, dose-escalation study to be followed by a phase II, open-label study. (Note: Study progression to phase II did not occur.)
Patients receive temsirolimus intravenous (IV) over 30 minutes on days 1, 8, 15, and 22 and oral sorafenib once or twice daily on days 1-28. Treatment course repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3-6 months.
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Kevin Kim||M.D. Anderson Cancer Center|