Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

COL-3 in Treating Patients With HIV-Related Kaposi's Sarcoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over NCI AMC-027 NCT00020683, AMC-027

Objectives

1. Compare the tumor response rate and duration of response in patients with HIV-related Kaposi's sarcoma treated with 2 different doses of COL-3.
2. Determine the biologic activity of this drug by measuring the percent of apoptotic cells in tumor biopsies of these patients before and after study therapy.
3. Determine the effect of this drug on the serum levels of matrix metalloproteinase (MMP)-2 and MMP-9 in these patients.
4. Compare the safety and toxicity of these regimens in these patients.
5. Evaluate the quality of life of patients treated with these regimens.
6. Evaluate the relationship between clinical response and quantitative measures of Kaposi's sarcoma-associated herpes virus/human herpes virus-8 and HIV viral load in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically proven Kaposi's sarcoma (KS) involving the skin, lymph nodes, oral cavity, gastrointestinal (GI) tract, and/or lungs
  • GI or pulmonary involvement must be asymptomatic or minimally symptomatic



• At least 5 measurable, cutaneous lesions that can be used as indicator lesions



• HIV positive by ELISA, Western Blot, or other federally approved, licensed HIV test

Prior/Concurrent Therapy:

Biologic therapy:

• At least 4 weeks since prior blood products
• At least 2 weeks since prior filgrastim (G-CSF) or epoetin alfa

Chemotherapy:

• At least 3 weeks since prior antineoplastic treatment for KS and recovered
• No concurrent systemic chemotherapy for KS
• No concurrent systemic chemotherapy for other neoplasia

Endocrine therapy:

• Concurrent oral contraceptives, megestrol, or testosterone allowed

Radiotherapy:

• No prior radiotherapy to indicator lesions
• No concurrent radiotherapy for KS

Surgery:

• Not specified

Other:

• No prior local therapy to any KS indicator lesion unless there is clear evidence of progression
• At least 2 weeks since prior acute treatment for infection or other serious medical illness
• Prior highly active antiretroviral therapy (HAART) allowed
• Concurrent HAART allowed if on optimal, stable regimen for a minimum of 4 weeks before study
• Concurrent antipyretics, analgesics, allergy medications, antidepressants, or sleep medications allowed
• Concurrent vitamins, acupuncture, or visual techniques allowed
• No other concurrent investigational drugs
• No other concurrent therapy for KS
• No concurrent rifampin, phenytoin, or phenobarbital

Patient Characteristics:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• At least 3 months

Hematopoietic:

• Hemoglobin at least 8.0 g/dL
• Absolute neutrophil count at least 750/mm³
• Platelet count at least 75,000/mm³
• No prior noniatrogenic bleeding disorder

Hepatic:

• AST and ALT no greater than 2.5 times upper limit of normal
• Total bilirubin normal (less than 3.5 mg/dL if elevation secondary to indinavir, and direct bilirubin normal)
• PT and PTT less than 1.2 times normal

Renal:

• Creatinine no greater than 1.5 mg/dL

  OR

• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• No evidence of prior myocardial infarction or cardiac ischemia

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study
• No active opportunistic infection

Expected Enrollment

A total of 70 patients (35 per treatment arm) will be accrued for this study within 1.75 years.

Outline

This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive low-dose oral COL-3 once daily.



• Arm II: Patients receive high-dose oral COL-3 once daily.

Treatment on both arms continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed.

Patients are followed for at least 1 month.

Dezube BJ, Krown SE, Lee JY, et al.: Randomized phase II trial of matrix metalloproteinase inhibitor COL-3 in AIDS-related Kaposi's sarcoma: an AIDS Malignancy Consortium Study. J Clin Oncol 24 (9): 1389-94, 2006.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

AIDS Associated Malignancies Clinical Trials Consortium

Bruce Dezube, MD, Protocol chair		Ph: 617-632-9258 Email: bdezube@bidmc.harvard.edu

Registry Information
Official Title		A Phase II Trial of COL-3 in Patients with HIV Related Kaposi's Sarcoma
Trial Start Date		2001-04-30
Registered in ClinicalTrials.gov		NCT00020683
Date Submitted to PDQ		2001-05-03
Information Last Verified		2002-08-30
NCI Grant/Contract Number		U01-CA70019