Official Title: “A Phase II Trial of Topical Halofuginone in Patients With HIV Related Kaposi's Sarcoma”

RATIONALE: Topical halofuginone hydrobromide ointment may stop the growth of Kaposi's sarcoma by stopping blood flow to the tumor.

PURPOSE: This randomized phase II trial is studying how well topical halofuginone hydrobromide works in treating patients with HIV-related Kaposi's sarcoma.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control

OBJECTIVES: - Compare the tumor response rate in patients with HIV-related Kaposi's sarcoma treated with topical halofuginone hydrobromide vs placebo. - Compare the safety and tolerability of these treatments in these patients. - Determine the ability of halofuginone hydrobromide to inhibit expression of MMP-2 and collagen type I in these patients. - Correlate CD4 and CD8 counts, HIV viral load, and HHV-8 viral load with response in patients treated with this drug. - Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a randomized, double-blind, multicenter study, with subsequent open-label treatment in stable or responding patients. Twelve treatable Kaposi's sarcoma lesions are selected on each patient, and these 12 lesions are randomized equally to 1 of 2 treatment arms (6 lesions receive study treatment and 6 lesions receive placebo); each patient serves as his/her own control. - Arm I: Patients apply topical halofuginone hydrobromide ointment to each of 6 lesions twice a day for 12 weeks. - Arm II: Patients apply topical placebo ointment to each of 6 lesions twice a day for 12 weeks.

Patients with stable or responding disease in either or both groups of treated lesions (halofuginone hydrobromide ointment or placebo ointment) may receive open-label treatment with topical halofuginone hydrobromide ointment to all 12 lesions for an additional 12 weeks as above in the absence of disease progression or unacceptable toxicity.

Patients are followed for at least 1 month.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 1 year.

Primary:

• Response rate by tumor evaluation every 4 weeks
• Safety and tolerability every 4 weeks

Secondary:

• Expression of MMP-2 and collagen type I in tumor biopsies as measured by in situ hybridization at baseline, day 29, and day 85
• Pharmacokinetics at week 8

DISEASE CHARACTERISTICS:

• Histologically proven Kaposi's sarcoma (KS)
• At least 14 cutaneous lesions, 12 of which are bidimensionally measurable and can serve as marker lesions
• Each lesion must measure at least 0.5 cm in diameter
• Serologically confirmed HIV infection
• No known active visceral KS
• No symptomatic KS-related edema that interferes with function or requires cytotoxic therapy

PATIENT CHARACTERISTICS:

• Age
• 16 and over
• Performance status
• Karnofsky 60-100%
• Life expectancy
• At least 3 months
• Hematopoietic
• Absolute neutrophil count at least 750/mm^3
• Platelet count at least 75,000/mm^3
• Hemoglobin at least 8 g/dL
• Hepatic
• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• Elevated bilirubin secondary to indinavir therapy allowed provided total bilirubin is no greater than 3.5 mg/dL and direct bilirubin is normal
• AST and ALT no greater than 3 times ULN
• Renal
• Creatinine less than 1.5 times ULN OR
• Creatinine clearance at least 60 mL/min
• Other
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 3 months after study participation
• No acute, active, untreated opportunistic infection within the past 14 days
• Oral thrush or genital herpes allowed
• No other serious medical illness within the past 14 days
• No concurrent neoplasm requiring cytotoxic therapy

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• More than 4 weeks since prior biological therapy for KS
• Chemotherapy
• More than 4 weeks since prior chemotherapy for KS
• No concurrent anticancer systemic cytotoxic chemotherapy
• Endocrine therapy
• No concurrent corticosteroids
• Replacement doses allowed
• Radiotherapy
• More than 4 weeks since prior radiotherapy for KS
• Surgery
• Not specified
• Other
• More than 60 days since prior local therapy for any KS-indicator lesion unless the lesion has clearly progressed since treatment
• More than 14 days since prior acute treatment for an infection (other than oral thrush or genital herpes)
• More than 4 weeks since prior local therapy for KS
• More than 4 weeks since prior investigational therapy for KS
• More than 4 weeks since other prior anticancer treatment for KS
• No other concurrent investigational agents other than IND-approved antiretroviral agents available under expanded access or compassionate use protocols
• No other concurrent KS-specific treatment
• Concurrent antiretroviral therapy allowed provided patient is on a stable regimen for at least 12 weeks prior to study entry and shows no evidence of ongoing KS regression (i.e., less than 25% decrease in the size, number, or nodularity of lesions, in the investigator's opinion)

Lead Sponsor: AIDS Associated Malignancies Clinical Trials Consortium

UCSF Comprehensive Cancer Center

San Francisco California 94115 United States

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles California 90089-9181 United States

Leahi Hospital

Honolulu Hawaii 96816 United States

Tulane Cancer Center at Tulane University Hospital and Clinic

New Orleans Louisiana 70112-2699 United States

Beth Israel Deaconess Medical Center

Boston Massachusetts 02215 United States

Herbert Irving Comprehensive Cancer Center at Columbia University

New York New York 10032 United States

Memorial Sloan-Kettering Cancer Center

New York New York 10021 United States

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University

Columbus Ohio 43210-1240 United States

Case Comprehensive Cancer Center

Cleveland Ohio 44106-5065 United States

Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center

Seattle Washington 98111 United States

Overall Clinical Trial Officials and Contacts

Susan E. Krown, MD Study Chair Memorial Sloan-Kettering Cancer Center  

Information obtained from ClinicalTrials.gov on May 11, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00064142

Study ID Number: CDR0000309055

ClinicalTrials.gov Identifier: NCT00064142

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database

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