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

NCT00450320 | Completed Phase 1

• 4 other identifiers: AMC-051U01CA070019CDR0000536481WYETH-0468X-4420
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 3

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.

Conditions

Sarcoma

Keywords

AIDS-related Kaposi sarcoma; recurrent Kaposi sarcoma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Clinical response

  Days 1, 29, 57, 85, every 28 days thereafter, at treatment discontinuation, and at study discontinuation.

• 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

• 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

• Effect of sirolimus on T-lymphocyte subsets

  Baseline, Days 29, 113, and at treatment discontinuation

Study Arms (1)

Rapamycin

ACTIVE COMPARATOR

The target rapamycin trough level will be 5-10 ng/mL. The initial dose will be dependent upon the type of HAART regimen.

Drug: sirolimus

Interventions

sirolimus DRUG

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.

Also known as: rapamycin

Rapamycin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• AIDS Malignancy Consortium: lead
• National Cancer Institute (NCI): collaborator
• The Emmes Company, LLC: collaborator

Study Sites (3)

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, 92093-0658, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Sarcoma; AIDS-related Kaposi sarcoma; Sarcoma, Kaposi

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Neoplasms, Vascular Tissue

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Susan E. Krown, MD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

• Dirk Dittmer, PhD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2007
• First Posted: March 22, 2007
• Study Start: October 1, 2007
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: August 29, 2014

Record last verified: 2014-08

Locations

US (3)