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

PURPOSE: Randomized phase II trial to study the effectiveness of topical halofuginone hydrobromide in treating patients who have HIV-related Kaposi's sarcoma.

Condition	Treatment or Intervention	Phase
epidemic Kaposi's sarcoma recurrent Kaposi's sarcoma	Drug: halofuginone hydrobromide  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: growth factor antagonist therapy	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  16 Years and above,  Genders Eligible for Study:  Both

Criteria

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 less 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)

California
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94143-0324,  United States; Recruiting
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033-1048,  United States; Recruiting
Hawaii
      Leahi Hospital, Honolulu,  Hawaii,  96816,  United States; Recruiting
Louisiana
      Tulane Cancer Center at Tulane University Hospital and Clinic, New Orleans,  Louisiana,  70112-2699,  United States; Recruiting
Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States; Recruiting
New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States; Recruiting
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States; Recruiting
      Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University, Cleveland,  Ohio,  44106-5065,  United States; Recruiting
Washington
      Cancer Institute at Virginia Mason Medical Center, Seattle,  Washington,  98111,  United States; Recruiting

Study chairs or principal investigators

Susan E. Krown, MD,  Study Chair,  Memorial Sloan-Kettering Cancer Center   
Henry Koon, MD,  Beth Israel Deaconess Medical Center   
Merrill J. Egorin, MD,  University of Pittsburgh Cancer Institute   

Study ID Numbers:  CDR0000309055; AMC-036; CWRU-040332; NCT00064142
Record last reviewed:  October 2004
Last Updated:  March 3, 2005
Record first received:  July 8, 2003
ClinicalTrials.gov Identifier:  NCT00064142
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08