This phase II trial studies how well halofuginone hydrobromide works in treating patients with human immunodeficiency virus (HIV)-related Kaposi's sarcoma. Halofuginone hydrobromide ointment may stop the growth of Kaposi's sarcoma by stopping blood flow to the tumor.
PRIMARY OBJECTIVES: I. To determine the tumor response rate of acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma to topical halofuginone (halofuginone hydrobromide) versus vehicle control. II. To evaluate the safety and tolerability of topical halofuginone and vehicle in patients with AIDS-related Kaposi's sarcoma. SECONDARY OBJECTIVES: I. To determine the ability of topical halofuginone to inhibit expression of matrix metallopeptidase 2 (MMP-2) and Collagen type I in AIDS-related Kaposi's sarcoma. II. To explore the relationship between baseline cluster of differentiation (CD) 4 and CD8 counts, HIV viral load and human herpesvirus 8 (HHV-8) viral load and response to halofuginone. III. To characterize the pharmacokinetics of halofuginone. OUTLINE: 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
30
AIDS - Associated Malignancies Clinical Trials Consortium
Rockville, Maryland, United States
Response rate
McNemar's chi-square test will be used to compare vehicle control and halofuginone with respect to response rates.
Time frame: Up to 30 days
Safety of topical halofuginone as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
McNemar's chi-square test will be used to compare the two treatments with respect to the incidence of specific adverse events.
Time frame: Up to 30 days after completion of treatment
Change in MMP-2 and collagen type I levels
Time frame: From baseline to 4 weeks
Change in MMP-2 and collagen type I levels
Changes from baseline in MMP-2 and Collagen type I for halofuginone and vehicle control lesions will be compared using the Wilcoxon rank sum test.
Time frame: From baseline to 12 weeks
Relationship of CD4, CD8, HIV viral load and HHV-8 viral load on response
Logistic regression analysis will be used.
Time frame: Up to 30 days
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