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A Pilot Study of Rapamycin in Patients With HIV-Related Kaposi's Sarcoma

Phase 1
18 Years
Not Enrolling

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Trial Information

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.

Inclusion Criteria


- Biopsy-proven Kaposi's sarcoma (KS) involving 1 or more of the following tissues:

- Skin

- Lymph nodes

- Oral cavity

- Gastrointestinal tract and/or lungs, if the disease meets the following

- Asymptomatic or minimally symptomatic

- Require systemic cytotoxic therapy

- At least five measurable, previously non-irradiated, cutaneous lesions (indicator

- Three non-indicator cutaneous lesions ≥ 4 x 4 mm accessible for 3-mm punch

- Serologic documentation of HIV infection (i.e., positive enzyme-linked immunosorbent
assay, positive western blot, or other federally approved licensed HIV test, or a
detectable blood level of HIV RNA)

- CD4 count > 50 cells/µL

- Serum HIV RNA level < 400 copies/mL

- KS that is either stable or progressing in the 4 weeks prior to study entry after
being on stable antiretroviral therapy for ≥ 12 weeks with a PI-based or NNRTI-based
regimen of ≥ 3 drugs, with no intention to change the regimen within 8 weeks of
starting study drug


- Karnofsky performance status 70-100%

- Life expectancy ≥ 3 months

- Hemoglobin ≥ 8.0 g/dL

- Absolute neutrophil count ≥ 1,000/mm³

- Platelet count ≥ 75,000/mm³

- Glomerular filtration rate > 40 mL/min

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 3.5 mg/dL if due to
indinavir therapy and direct bilirubin normal; no limit if due to atazanavir therapy
and direct bilirubin is normal)

- AST and ALT ≤ 2.5 times ULN

- Fasting triglyceride ≤ 400 mg/dL (4.5 mmol/L)

- Total cholesterol ≤ 300 mg/dL (7.8 mmol/L)

- Spot urine protein:creatinine ratio ≤ 0.5 and/or proteinuria ≤ 500 mg

- No other prior or concurrent malignancy except for treated basal cell skin cancer or
carcinoma in situ of the cervix

- No evidence of infiltrate, cavitation, or consolidation (i.e., due to infection or
other serious medical illness) on chest x-ray within the past 3 months

- No known hypersensitivity to sirolimus or its derivatives or macrolide antibiotics

- No New York Heart Association class III-IV cardiac disease (e.g., myocardial
infarction within the past 6 months)

- No other concurrent severe and/or life-threatening medical disease

- No acute or known chronic liver disease (e.g., chronic active hepatitis or cirrhosis)

- Hepatitis C with documentation of no or minimal fibrosis on liver biopsy allowed

- No concurrent active opportunistic infection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier-method contraception during and for 3
months after completion of study therapy


- No prior sirolimus

- No acute treatment for infection or other serious medical illness within the past 14

- No anticancer therapy for KS, including chemotherapy, radiotherapy, or biological
therapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C)

- No local therapy for any KS indicator lesion within the past 60 days, unless the
lesion has progressed since treatment

- No investigational therapies within the past 4 weeks

- No major surgery within the past 2 weeks

- No prior or concurrent treatment with agents or medications, other than
antiretroviral drugs used to treat HIV infection, that would interfere with the
metabolism or excretion of sirolimus, including, but not limited to, the following:

- Antifungals (e.g., voriconazole, itraconazole, or ketoconazole)

- Antibiotics (e.g., erythromycin, telithromycin, clarithromycin, rifampin, or

- Cidofovir

- Cisapride

- Diltiazem

- Cyclosporine

- Grapefruit juice

- Hypericum perforatum (St. John's wort)

- No other concurrent anticancer therapies, including chemotherapy, biological therapy,
or radiotherapy

- No concurrent systemic corticosteroid treatment, other than replacement doses

- No other concurrent investigational therapies

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and toxicity

Outcome Time Frame:

All study visits

Safety Issue:


Principal Investigator

Susan E. Krown, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Federal Government

Study ID:




Start Date:

October 2007

Completion Date:

September 2009

Related Keywords:

  • Sarcoma
  • AIDS-related Kaposi sarcoma
  • recurrent Kaposi sarcoma
  • Sarcoma, Kaposi
  • Sarcoma



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