Bethesda, Maryland 20892

  • Sarcoma

Purpose:

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.


Criteria:

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


NCT ID:

NCT00304122


Primary Contact:

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


Backup Contact:

N/A


Location Contact:

Bethesda, Maryland 20892
United States

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

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: December 07, 2022

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