Sirolimus in Treating Patients With HIV-Related Kaposi's Sarcoma
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Rapamycin in Patients With HIV-Related Kaposi's Sarcoma|
- Safety and toxicity [ Time Frame: All study visits ] [ Designated as safety issue: Yes ]
- Dose of sirolimus required to achieve target trough sirolimus plasma concentration [ Time Frame: Days 8, 15, 21, 29, 43, 57, 85, 113, and every 28 days thereafter ] [ Designated as safety issue: No ]
- Clinical response [ Time Frame: Days 1, 29, 57, 85, every 28 days thereafter, at treatment discontinuation, and at study discontinuation. ] [ Designated as safety issue: No ]
- Effect of sirolimus on mTOR-dependent signaling in peripheral blood mononuclear cells (PBMC) and Kaposi's sarcoma (KS) tumor biopsies [ Time Frame: baseline, days 1, 15, 29, 57, 113, every 28 days thereafter, study discontinuation ] [ Designated as safety issue: No ]
- Serum cytokine profile [ Time Frame: baseline, days 1, 15, 29, 57, 113, every 28 days thereafter, study discontinuation ] [ Designated as safety issue: No ]
- Effect of sirolimus on HIV and KS-associated herpesvirus viral loads [ Time Frame: Days 1, 15, 29, 57, 113, every 28 days thereafter, study discontinuation ] [ Designated as safety issue: No ]
- Effect of sirolimus on T-lymphocyte subsets [ Time Frame: Baseline, Days 29, 113, and at treatment discontinuation ] [ Designated as safety issue: No ]
|Study Start Date:||October 2007|
|Study Completion Date:||September 2009|
|Primary Completion Date:||September 2009 (Final data collection date for primary outcome measure)|
Active Comparator: Rapamycin
The target rapamycin trough level will be 5-10 ng/mL. The initial dose will be dependent upon the type of HAART regimen.
The target rapamycin trough level will be 5-10 ng/mL. The initial dose will be dependent upon the type of HAART regimen. Subjects will continue on study protocol for six cycles as long as their KS is stable or continuing to respond to study medication. Treatment will be extended for up to six additional cycles if the subject has met criteria for a response. Subjects with no more than stable disease will have treatment discontinued after six cycles. Protocol treatment will be discontinued if the subject develops tumor progression, unacceptable toxicity or develops one of the protocol-defined reasons for treatment discontinuation at any time during the study.
Other Name: rapamycin
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00450320
|United States, California|
|Rebecca and John Moores UCSD Cancer Center|
|La Jolla, California, United States, 92093-0658|
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Study Chair:||Susan E. Krown, MD||Memorial Sloan-Kettering Cancer Center|
|Principal Investigator:||Dirk Dittmer, PhD||UNC Lineberger Comprehensive Cancer Center|