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.

PURPOSE: This phase II trial is studying how well sorafenib works in treating patients with stage IV melanoma.

Condition	Intervention	Phase
Stage IV Melanoma	Drug: sorafenib  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the efficacy of sorafenib, in terms of anti-tumor effects and proportion of clinical responses, in patients with previously untreated stage IV malignant melanoma.

Secondary

• Correlate the efficacy of this drug with the presence of mutant or wild-type BRAF gene in tumors of these patients.
• Determine the toxicity profile of this drug in these patients.
• Correlate serum cryptic collagen epitopes with the extent of tumor burden, invasion, and metastasis in patients treated with this drug.
• Determine the potential of serum cryptic collagen epitopes to serve as a surrogate marker for monitoring the course of disease in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to presence of BRAF gene mutation in tumor sample (yes vs no).

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed annually.

PROJECTED ACCRUAL: A total of 26-74 patients (13-37 per stratum) will be accrued for this study within 5.2-18.5 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed malignant melanoma
• Stage IV disease
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 20 mm by conventional techniques OR > 10 mm by spiral CT scan
• Disease amenable to biopsy (first 13 patients in each stratum only)
• Brain metastases allowed provided the following criteria are met:
• Disease has remained radiologically stable for ≥ 6 weeks after completion of whole-brain radiotherapy and remains stable at the time of study entry
• No mass effect present by radiology
• No requirement for steroid therapy to control symptoms of brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No evidence of bleeding diathesis

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Bilirubin ≤ 2 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No uncontrolled hypertension
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No psychiatric illness that would preclude study compliance
• No pre-existing non-hematolgical dysfunction ≥ grade 2
• No ongoing or active infection
• No history of serious allergic reaction to eggs
• Able to swallow pills
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or other non-invasive carcinoma
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• See Disease Characteristics

Surgery

• Not specified

Other

• No prior therapy for metastatic melanoma
• No other concurrent investigational agents
• No concurrent therapeutic anticoagulation
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer therapy

Please refer to this study by ClinicalTrials.gov identifier  NCT00119249

New York
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting
      NYU Cancer Institute at New York University Medical Center, New York,  New York,  10016,  United States; Recruiting
Australia, New South Wales
      Sydney Cancer Centre at Royal Prince Alfred Hospital, Sydney,  New South Wales,  2050,  Australia; Recruiting

Study chairs or principal investigators

Anna Pavlick, MD,  Study Chair,  New York University School of Medicine   

Study ID Numbers:  CDR0000434613; NYWCCC-NYU-0438; NCI-6617; NCT00119249
Record last reviewed:  July 2005
Last Updated:  July 25, 2005
Record first received:  July 12, 2005
ClinicalTrials.gov Identifier:  NCT00119249
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-07-26