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 temosirolimus may kill more tumor cells.
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose of temsirolimus when administered with sorafenib in patients with metastatic, recurrent, or unresectable melanoma. II. To determine the safety and toxicity of this regimen in these patients. SECONDARY OBJECTIVES: I. To Determine the population pharmacokinetics of this regimen in these patients. II. 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 followed by a phase II, open-label study (2005-0215). Patients receive temsirolimus 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
69
Given orally
Given IV
M D Anderson Cancer Center
Houston, Texas, United States
Maximum tolerated dose of CCI-779 in combination with BAY43-9006 (Phase I) determined by DLT assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)
Time frame: 28 days
Objective response rate (complete response and partial response) CCI-779 in combination with BAY43-9006 (Phase II)
Time frame: Up to 5 years
Progression-free survival
Kaplan-Meier life table methods and Cox proportional hazards regression modeling will be utilized to analyze progression-free survival and overall 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
Overall survival
Kaplan-Meier life table methods and Cox proportional hazards regression modeling will be utilized to analyze progression-free survival and overall survival.
Time frame: 5 years
Noncompartmental pharmacokinetic parameters of BAY43-9006 and CCI-779 estimated using a validated commercial software
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).
Time frame: Week 1 and 3
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