NCT00811759

Sorafenib and Temozolomide in Treating Patients With Stage III or Stage IV Melanoma

Open-label, Single Center, Uncontrolled Phase I/II Study Evaluating the Safety and Maximum Tolerated Dose of Daily Sorafenib Administered in Combination With Prolonged Temozolomide in Patients With Metastatic Melanoma

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 58 (estimated)
• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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 temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with temozolomide may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of giving sorafenib together with temozolomide in treating patients with stage III or stage IV melanoma.

Detailed description

OBJECTIVES: Primary * Determine the safety profile and the maximum tolerated dose of sorafenib tosylate and temozolomide in patients with stage III-IV melanoma. (Phase I) * Evaluate progression-free survival at 12 weeks. (Phase II) Secondary * Evaluate tumor response according to RECIST criteria. * Evaluate overall and progression-free survival. * Evaluate the effect of treatment on tumor vascularization. * Compare the pharmacokinetic profile of temozolomide with and without sorafenib tosylate. * Evaluate the number and the role of lymphocytes. * Correlate tumor response rate with BRAF mutation status. * Correlate response rate with MGMT activity. * Compare the efficacy of genomics and proteomics as a means of discovery of serum biomarkers. * Study the prognostic and predictive value of circulating endothelial cells and circulating endothelial progenitors. OUTLINE: This is a phase I dose-escalation study followed by a phase II study. Patients receive oral sorafenib tosylate twice daily on days 1-28 (days 8-28 of course 1) and oral temozolomide once daily on days 1-7 and 15-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with accessible tumors (cutaneous or sub-cutaneous) undergo biopsies at baseline and day 28 for analysis of BRAF mutations and MGMT expression.

Conditions

• Melanoma (Skin)

Interventions

Type	Name	Description
DRUG	sorafenib tosylate
DRUG	temozolomide
GENETIC	gene expression analysis
GENETIC	mutation analysis
OTHER	laboratory biomarker analysis
OTHER	pharmacological study
PROCEDURE	biopsy

Timeline

• Start date: 2007-06-01
• Primary completion: 2009-05-01
• First posted: 2008-12-19
• Last updated: 2010-10-07

Locations

1 site across 1 country: France