Sirolimus in Treating Patients With HIV-Related Kaposi's Sarcoma

• Status: Completed
• Trial end date: 2009-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AIDS Malignancy Consortium
• Collaborators: National Cancer Institute (NCI); The Emmes Company, LLC; The EMMES Corporation
• Treatments: Everolimus; Sirolimus

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