A Pilot Study of Rapamycin in Patients With HIV-Related Kaposi's Sarcoma
- Determine the safety and toxicity of sirolimus in patients with HIV-related Kaposi's
sarcoma (KS) receiving protease inhibitor (PI)-based or nonnucleoside reverse
transcriptase inhibitor (NNRTI)-based highly active antiretroviral treatment (HAART)
- Estimate the dose(s) of this drug required to achieve target trough sirolimus plasma
concentrations of 5-10 ng/mL in patients receiving PI-based or NNRTI-based HAART
- Evaluate the clinical response of KS in patients treated with this sirolimus.
- Determine the effects of this drug on mTOR-dependent signaling in peripheral blood
mononuclear cells (PBMC) and KS tumor biopsies.
- Determine the serum cytokine profiles pre- and post-treatment with this drug.
- Determine the effects of this drug on HIV and KS-associated herpesvirus (KSHV) viral
- Determine the effects of this drug on T-lymphocyte subsets.
OUTLINE: This is a multicenter study. Patients are assigned to 1 of 3 treatment groups.
- Group 1 (patients receiving PI-based HAART regimen with ritonavir): Patients receive
oral sirolimus 0.0015 mg/kg/day once daily on days 1-28 for 6 courses as long as KS is
stable or the disease is continuing to respond to treatment. Patients may receive 6
additional courses provided they meet criteria for response in the absence of disease
progression or unacceptable toxicity. Patients with no more than stable disease after 6
courses are discontinued from treatment.
- Group 2 (patients receiving PI-based HAART regimen without ritonavir): Patients receive
oral sirolimus 0.003 mg/kg/day as in group 1.
- Group 3 (patients receiving NNRTI-based HAART regimen): Patients receive oral sirolimus
0.05 mg/kg/day as in group 1.
Blood samples are collected periodically and analyzed for sirolimus levels via LCMSMS.
PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety and toxicity
All study visits
Susan E. Krown, MD
Memorial Sloan-Kettering Cancer Center
United States: Federal Government
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|Beth Israel Deaconess Medical Center||Boston, Massachusetts 02215|
|Rebecca and John Moores UCSD Cancer Center||La Jolla, California 92093-0658|