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
- 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)
- 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
- 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
- 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.
Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (Phase I)
Caroline Robert, MD
Gustave Roussy, Cancer Campus, Grand Paris
United States: Federal Government