Sorafenib and Isolated Limb Infusion of Melphalan in Treating Patients With Stage III Melanoma of the Arm or Leg
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib may also make tumor cells more sensitive to melphalan. Giving sorafenib together with an isolated limb infusion of melphalan may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of sorafenib when given together with an isolated limb infusion of melphalan in treating patients with stage III melanoma of the arm or leg.
Drug: sorafenib tosylate
Genetic: gene expression analysis
Genetic: protein expression analysis
Genetic: western blotting
Other: pharmacological study
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Dose Escalation Trial to Evaluate Safety and Efficacy of Oral Sorafenib (Nexavar) With Regional Melphalan Via Normothermic Isolated Limb Infusion (ILI) in Patients With Intransit Extremity Melanoma|
- Maximum tolerated dose [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Safety and tolerability [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Antitumor activity, as evidenced by best overall response and duration of response [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Duration of progression-free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Pharmacokinetics of melphalan [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Tumor gene and protein expression profiles following treatment [ Time Frame: 3 years ] [ Designated as safety issue: No ]
|Study Start Date:||October 2007|
|Primary Completion Date:||August 2009 (Final data collection date for primary outcome measure)|
|Experimental: Sorafenib dose escalation||Drug: melphalan Drug: sorafenib tosylate Genetic: gene expression analysis Genetic: protein expression analysis Genetic: western blotting Other: pharmacological study|
- To determine the dose-limiting toxicities and maximum tolerate dose of systemic sorafenib tosylate in combination with regionally administered melphalan by isolated limb infusion in patients with stage IIIB or IIIC intransit extremity melanoma.
- To characterize the safety and tolerability of this regimen in these patients.
- To assess the antitumor activity of this regimen, as evidenced by best overall response and duration of response, in these patients.
- To characterize the duration of progression-free survival of these patients.
- To characterize the pharmacokinetics of melphalan.
- To assess alterations in selected gene and protein expression profiles following treatment.
OUTLINE: This is a multicenter, dose-escalation study of sorafenib tosylate.
Patients receive oral sorafenib tosylate twice daily on days 1-14 and melphalan via isolated limb infusion into the upper or lower extremities on day 8.
Patients undergo tumor biopsies at baseline and in weeks 2 and 12 for gene expression analysis and western blot analysis. Patients also undergo blood sample collection periodically for pharmacokinetic analysis of melphalan.
After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 2 years.
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Douglas S. Tyler, MD||Duke Cancer Institute|