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
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
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.
OBJECTIVES:
Primary
Secondary
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.
DISEASE CHARACTERISTICS:
Diagnosis of unresectable or metastatic melanoma
Previously treated or untreated metastatic disease
At least one unidimensionally measurable lesion by RECIST criteria by scan or MRI
No concurrent brain or CNS metastases
PATIENT CHARACTERISTICS:
WHO performance status 0-1
Life expectancy ≥ 3 months
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin > 9 g/dL
PT, INR, and PTT < 1.5 times upper limit of normal (ULN)
Transaminases < 2.5 times ULN (< 5 in the case of liver metastases)
Amylase and lipase < 1.5 times ULN
Bilirubin ≤ 1.5 times ULN
Serum creatinine < 1.5 times ULN
Normal respiratory, cardiac, and neurological function
Not pregnant or nursing
No history of any of the following cardiac conditions:
No severe active infection > grade 2
No epilepsy requiring medical treatment
No other cancer except for carcinoma in situ of the cervix, basal cell carcinoma, superficial bladder tumors, or curatively treated cancer > 3 years ago
No HIV or hepatitis B or C positivity
No lactase or galactokinase deficiency, galactose intolerance, or disease accompanied by malabsorption of glucose or galactose
No allergy to the study drugs or to dacarbazine
Able to swallow medications
No patients deprived of liberty
No psychological, familial, social, or geographic conditions that would preclude clinical follow up
PRIOR CONCURRENT THERAPY: