A Phase I Study of TNP-470 in the Treatment of AIDS-Associated Kaposi's Sarcoma

• Status: Completed
• Trial end date: 1997-02-01
• Target enrollment: 0
• Participant gender: All

Summary

To assess toxicity and determine the MTD of intravenous TNP-470 administered weekly in patients with AIDS-related Kaposi's sarcoma. To assess pharmacokinetics and tumor response of the drug.

Since evidence shows that neovascularization is important in the development of Kaposi's sarcoma, drugs that inhibit angiogenesis, such as TNP-470, may be of benefit in patients with the disease.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: O-(Chloroacetylcarbamoyl)fumagillol

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• AZT, ddI, ddC, or d4T provided patients have received at least 2 weeks of this therapy prior to study entry. (Combination ddI/ddC is not permitted.)

• MAI prophylaxis.

Required in patients with CD4 count < 200 cells/mm3:

Aerosolized pentamidine, trimethoprim/sulfamethoxazole, or dapsone as PCP prophylaxis.

Patients must have:

• HIV infection.

• Cutaneous Kaposi's sarcoma.

• Life expectancy of at least 3 months.

• Consent of parent or guardian if under 18 years of age.

NOTE:

• This protocol is considered suitable for prison populations.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Peripheral neuropathy (grade 2 or worse).

• Underlying severe or life-threatening infection with bacterial, viral, fungal, or protozoal pathogens.

• Known hypersensitivity to TNP-470, fumagillin, or known related compounds.

PER AMENDMENT 9/3/96:

• Cataracts.

Concurrent Medication:

Excluded:

• Combination therapy with ddI/ddC (although these drugs may be administered alone or in combination with AZT).

• Anticonvulsive medication.

• Steroids.

• Antineoplastic drugs.

• Interferons.

• Systemic or topical anti-Kaposi's sarcoma agents or regimens.

• Suramin.

• Aspirin.

• Warfarin.

• Heparin (including heparin flushes).

• Nonsteroidal anti-inflammatory drugs.

• Investigational status drugs.

Patients with the following prior conditions are excluded:

• History of substantial non-iatrogenic bleeding disorders.

• History of tumor or malignancies other than Kaposi's sarcoma, with the exception of completely resected basal cell skin carcinoma or in situ cervical carcinoma.

• History of seizures within the past 10 years.

PER AMENDMENT 9/3/96:

• History of cataracts.

Prior Medication:

Excluded within 4 weeks prior to study entry:

• Steroids.

• Antineoplastic drugs.

• Interferons.

• Systemic or topical anti-Kaposi's sarcoma agents or regimens.

Excluded within 6 months prior to study entry:

• Suramin.

Unwilling to refrain from unprotected sexual contact or other activities that may result in HIV re-infection.