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

Inclusion Criteria

DISEASE CHARACTERISTICS:

- 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
criteria:

- Asymptomatic or minimally symptomatic

- Require systemic cytotoxic therapy

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

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

- 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

PATIENT CHARACTERISTICS:

- 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

PRIOR CONCURRENT THERAPY:

- No prior sirolimus

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

- 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
rifabutin)

- 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