Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Topical Halofuginone Hydrobromide in Treating Patients With HIV-Related Kaposi's Sarcoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	16 and over	NCI	AMC-036 CWRU-040332, NCT00064142

Special Category: NCI Web site featured trial

Objectives

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

Entry 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

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)

Patient Characteristics:

Age

• 16 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count at least 750/mm³
• Platelet count at least 75,000/mm³
• 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

Expected Enrollment

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

Outcomes

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

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

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.

Trial Contact Information

Trial Lead Organizations

AIDS Associated Malignancies Clinical Trials Consortium

Susan Krown, MD, Protocol chair		Ph: 212-639-7426; 800-525-2225 Email: krowns@mskcc.org
Henry Koon, MD, Protocol co-chair		Ph: 617-667-9900
Merrill Egorin, MD, Protocol co-chair		Ph: 412-623-3252 Email: egorinmj@msx.upmc.edu

Related Information

Featured trial article

Registry Information
Official Title		A Phase II Trial of Topical Halofuginone in Patients with HIV Related Kaposi's Sarcoma
Trial Start Date		2003-05-20
Trial Completion Date		2008-03-13
Registered in ClinicalTrials.gov		NCT00064142
Date Submitted to PDQ		2003-05-22
Information Last Verified		2006-01-03
NCI Grant/Contract Number		CA70019

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