Sorafenib and Isolated Limb Infusion of Melphalan in Treating Patients With Stage III Melanoma of the Arm or Leg

DISEASE CHARACTERISTICS:

Histologically confirmed primary or recurrent extremity melanoma

Stage IIIB or IIIC disease

Patients with stage IIIC disease must have had regional lymph nodes previously removed
Disease to be treated by regional therapy must be distal to the planned site of tourniquet placement

Bidimensionally measurable disease by caliper or radiological method

Must have identifiable target lesions for disease assessment

Patients with a single lesion must have archived tumor tissue available for research analysis
No stage IV disease

No known brain metastasis

Patients with neurological symptoms must have undergone a CT scan or MRI of the brain within the past 4 weeks to exclude brain metastasis

PATIENT CHARACTERISTICS:

ECOG or Zubrod performance status 0-1
Life expectancy > 6 months
Hemoglobin ≥ 9.0 g/dL
WBC ≥ 3,000/mm^3
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
ALT and AST ≤ 2.5 x ULN
INR < 1.5 or PT/PTT normal
Creatinine ≤ 1.5 x ULN
Not pregnant or nursing
Negative serum pregnancy test
Fertile patients must use effective contraception
Must have a palpable femoral or axillary pulse in the extremity to be treated

No cardiac disease, including any of the following:

NYHA class III or IV congestive heart failure
Unstable angina (i.e., angina symptoms at rest) or new onset angina within the past 3 months
Myocardial infarction within the past 6 months
No cardiac ventricular arrhythmias requiring antiarrhythmic therapy
No uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 90 mm Hg, despite optimal medical management
No known HIV infection
No chronic hepatitis B or C
No active clinically serious infection > CTCAE grade 2
No thrombotic or embolic events (e.g., cerebrovascular accident or transient ischemic attacks) within the past 6 months
No signs or symptoms of vascular insufficiency (i.e., any history of blood clots or other ischemic peripheral vascular disease)
No evidence or history of bleeding diathesis or coagulopathy
No pulmonary hemorrhage or bleeding event ≥ CTCAE grade 2 within the past 4 weeks
No other hemorrhage or bleeding event ≥ CTCAE grade 3 within the past 4 weeks
No serious nonhealing wound, ulcer, or bone fracture
No significant traumatic injury within the past 4 weeks
No condition that impairs the patient's ability to swallow whole pills
No malabsorption problem
No known history of allergic reactions and/or hypersensitivity to melphalan, sorafenib tosylate, or any other agent used in the study
No psychiatric condition or diminished capacity that would compromise giving informed consent, or interfere with study compliance

No history of other malignancies, except for any of the following:

Adequately treated basal cell or squamous cell carcinoma of the skin
Curatively treated in situ carcinoma of the uterine cervix, prostate cancer, or superficial bladder cancer
Other curatively treated solid tumor with no evidence of disease for ≥ 5 years

PRIOR CONCURRENT THERAPY:

Recovered from prior therapy
No prior sorafenib tosylate
Prior melphalan via isolated limb infusion allowed
No antineoplastic therapy, radiotherapy, or any other investigational drug within the past 4 weeks
No major surgery or open biopsy within the past 4 weeks
No concurrent Hypericum perforatum (St. John wort) or rifampin
Concurrent anti-coagulation treatment with warfarin or heparin allowed