Sirolimus in Treating Patients With HIV-Related Kaposi's Sarcoma
- Registration Number
- NCT00450320
- Lead Sponsor
- AIDS Malignancy Consortium
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as sirolimus, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sirolimus also 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 pilot study is studying sirolimus in treating patients with HIV-related Kaposi's sarcoma.
- Detailed Description
OBJECTIVES:
Primary
* 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) regimens.
* 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 regimens.
Secondary
* 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 loads.
* 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 7
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Rapamycin sirolimus The target rapamycin trough level will be 5-10 ng/mL. The initial dose will be dependent upon the type of HAART regimen.
- Primary Outcome Measures
Name Time Method Safety and toxicity All study visits Dose of sirolimus required to achieve target trough sirolimus plasma concentration Days 8, 15, 21, 29, 43, 57, 85, 113, and every 28 days thereafter
- Secondary Outcome Measures
Name Time Method Effect of sirolimus on mTOR-dependent signaling in peripheral blood mononuclear cells (PBMC) and Kaposi's sarcoma (KS) tumor biopsies baseline, days 1, 15, 29, 57, 113, every 28 days thereafter, study discontinuation Effect of sirolimus on T-lymphocyte subsets Baseline, Days 29, 113, and at treatment discontinuation Clinical response Days 1, 29, 57, 85, every 28 days thereafter, at treatment discontinuation, and at study discontinuation. Serum cytokine profile baseline, days 1, 15, 29, 57, 113, every 28 days thereafter, study discontinuation Effect of sirolimus on HIV and KS-associated herpesvirus viral loads Days 1, 15, 29, 57, 113, every 28 days thereafter, study discontinuation
Trial Locations
- Locations (3)
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Rebecca and John Moores UCSD Cancer Center
🇺🇸La Jolla, California, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States