Phase I Study of Sorafenib in Patients With Kaposi's Sarcoma

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Alternate Title

Sorafenib in Treating Patients With Kaposi's Sarcoma

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase ITreatmentClosed18 and overNCINCI-06-C-0083
7048, NCI-7048, NCI-P6700, NCT00304122

Special Category: NCI Web site featured trial, NIH Clinical Center trial



  1. Assess the toxicity profile and pharmacokinetics of sorafenib in patients with HIV-related Kaposi's sarcoma (KS) who are receiving ritonavir.
  2. 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.


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

Entry 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

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

Patient Characteristics:

  • ECOG performance status ≤ 2
  • Life expectancy > 6 months
  • Hemoglobin > 9 g/dL
  • WBC > 1,000/mm3
  • Platelet count > 75,000/mm3
  • 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

Expected Enrollment


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


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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Robert Yarchoan, MD, Protocol chair
Ph: 301-496-8959

Related Information

Featured trial article
Web site for additional information

Registry Information

Official TitlePhase I and Pharmacokinetic Study of BAY 43-9006 (Sorafenib) in Patients with Kaposi's Sarcoma
Trial Start Date2006-07-03
Trial Completion Date2012-12-01 (estimated)
Registered in ClinicalTrials.govNCT00304122
Date Submitted to PDQ2006-01-30
Information Last Verified2009-07-05

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.