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