Bethesda, Maryland 20892

  • Sarcoma


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).

Study summary:

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



Primary Contact:

Study Chair
Robert Yarchoan, MD
NCI - HIV and AIDS Malignancy Branch

Backup Contact:


Location Contact:

Bethesda, Maryland 20892
United States

Clinical Trials Office - Warren Grant Magnusen Clinical Center
Phone: 888-NCI-1937

Site Status: Recruiting

Data Source:

Date Processed: December 07, 2022

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.

Click to view Full Listing

This study is not currently recruiting Study Participants on The form below is not enabled.