Sorafenib in Treating Patients With Kaposi's Sarcoma

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.