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 I trial is studying the side effects and best dose of sorafenib in treating patients with Kaposi's sarcoma (KS).

OBJECTIVES:

Primary

• Assess the toxicity profile and pharmacokinetics of sorafenib in patients with HIV-related Kaposi's sarcoma (KS) who are receiving ritonavir.
• Assess, in a preliminary manner, the pharmacokinetics and toxicity profile of sorafenib in patients with HIV-related or HIV-unrelated (classic) KS who are not receiving ritonavir.

Secondary

• Assess preliminary information on the antitumor effect of sorafenib in these patients.
• Obtain preliminary information regarding changes in blood flow of KS lesions in these patients.
• Assess changes induced by sorafenib in target receptor kinase phosphorylation and signaling molecules believed to be important in the pathogenesis of KS.
• Collect information on immunologic and virologic parameters related to KS-associated herpes virus infection, KS, and in patients with HIV-related KS, to HIV.
• Study the effects of sorafenib on angiogenic factors, including vascular endothelial growth factor and platelet-derived growth factor, in patients with KS.

OUTLINE: This is a dose-escalation, parallel group study . Patients are stratified according to concurrent ritonavir treatment (yes vs no) and HIV-related Kaposi's sarcoma (KS) (yes vs no).

Patients receive oral sorafenib once or twice daily on days 1-21. Treatment repeats every 21 days for up to 18 courses (54 weeks) in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients per stratum receive escalating doses of sorafenib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

After completion of study therapy, patients are followed at 3-6 weeks.

PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed Kaposi's sarcoma (KS)

  • HIV-related or HIV-unrelated (classic) KS

• Measurable disease, as defined by 1 of the following:

  • At least 5 measurable cutaneous KS lesions that have not been previously treated with local therapy
  • Other measurable noncutaneous disease that permits a response to be assessed

• Patients with HIV-related KS must be receiving and willing to comply with a highly active antiretroviral therapy (HAART) regimen that either utilizes ≥ 3 drugs OR attains suppression of HIV to below the limit of detection (50 copies HIV/mL)

  • HIV-related KS lesions must meet 1 of the following criteria:

    • Increasing during the 3 months prior to screening while the patient is receiving HAART or has unchanged suppression of HIV to below the limit of detection
    • Stable for at least 4 months while the patient is taking HAART
• No extensive, active, or symptomatic pulmonary KS
• No symptomatic visceral KS, except for that involving the oral cavity
• No KS that appears to be improving after other therapy

PATIENT CHARACTERISTICS:

• ECOG performance status ≤ 2
• Life expectancy > 6 months
• Hemoglobin > 9 g/dL
• WBC > 1,000/mm^3
• Platelet count > 75,000/mm^3
• PT and PTT ≤ 120% of control, unless lupus anticoagulant present
• Bilirubin ≤ 1.5 times upper limit of normal (ULN) (for patients not receiving protease inhibitor therapy) OR total bilirubin ≤ 3.7 mg/dL with a direct bilirubin fraction ≤ 0.2 mg/dL (for patients receiving protease inhibitor therapy)
• AST ≤ 2.5 times ULN
• Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min
• No known hypersensitivity to sorafenib
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

• No other prior or concurrent malignant tumors, except for the following:

  • Cancer in complete remission for ≥ 1 year from the time a response was first documented
  • Completely resected basal cell carcinoma
  • In situ squamous cell carcinoma of the cervix or anus
• No evidence of severe or life-threatening infection within the past 2 weeks
• Lipase ≤ 2 times ULN OR amylase ≤ 2 times ULN (unless documented to be of nonpancreatic origin or associated with macroamylasemia)

• No other abnormality that would be scored as ≥ grade 3 toxicity, except any of the following:

  • Lymphopenia
  • Direct manifestation of KS
  • Direct manifestation of HIV infection, except for neurologic or cardiac manifestations
  • Direct manifestation of HIV therapy, except for neurologic or cardiac manifestations
  • Asymptomatic hyperuricemia
• No evidence of bleeding diathesis
• No uncontrolled hypertension (i.e., diastolic blood pressure [BP] > 104 mm Hg or systolic BP > 159 mm Hg)

• No uncontrolled intercurrent illness, including, but not limited to, the following:

  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would limit compliance with study requirements
• No other condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

• No cytotoxic chemotherapy or other specific KS therapy (except for antiretroviral therapy) within the past 3 weeks
• No supraphysiologic doses of corticosteroids within the past 3 weeks
• No prior sorafenib

• No concurrent therapeutic anticoagulation

  • Concurrent prophylactic anticoagulation (e.g., low-dose warfarin) of venous or arterial access devices allowed provided PT and PTT requirements are met
• No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, and phenobarbital), rifampin, or Hypericum perforatum (St. John's Wort)
• No concurrent systemic glucocorticoids
• No concurrent cytokines except epoetin alfa or filgrastim (G-CSF)
• No concurrent cytotoxic chemotherapy, radiation therapy, topical therapy, or other specific therapy for KS