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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000763
First received: November 2, 1999
Last updated: March 30, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Sarcoma, Kaposi
HIV Infections
Drug: TNP-470
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Primary Purpose: Treatment
Official Title: A Phase I Study of TNP-470 in the Treatment of AIDS-Associated Kaposi's Sarcoma

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 42
Study Completion Date: February 1997
Detailed Description:

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.

Patients are entered at 7 escalating dose levels of TNP-470. (PER AMENDMENT 9/3/96: dose maximum level changed.) Four patients treated at a given dose level must receive at least 4 weeks of therapy before escalation in subsequent cohorts proceeds. If 50 percent of patients at a given dose level experience dose-limiting toxicity, the previous dose is defined as the MTD and an additional two patients are treated at the MTD. Patients receive treatment for 12 weeks, followed by 2 weeks of rest, followed by an additional 12 weeks of treatment. Patients are followed for 12 weeks post-treatment.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000763

Locations
United States, California
USC CRS
Los Angeles, California, United States, 90033
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
United States, Massachusetts
Beth Israel Deaconess - East Campus A0102 CRS
Boston, Massachusetts, United States, 02215
Bmc Actg Crs
Boston, Massachusetts, United States, 02118
United States, Missouri
Washington U CRS
St. Louis, Missouri, United States
United States, New York
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, United States
Sponsors and Collaborators
Investigators
Study Chair: Gill PS
Study Chair: Dezube B
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000763     History of Changes
Other Study ID Numbers: ACTG 215, 11192
Study First Received: November 2, 1999
Last Updated: March 30, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Sarcoma, Kaposi
Acquired Immunodeficiency Syndrome
Antineoplastic Agents

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Sarcoma
Sarcoma, Kaposi
AIDS-Related Opportunistic Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Herpesviridae Infections
DNA Virus Infections
Neoplasms, Vascular Tissue
Opportunistic Infections
Infection
Parasitic Diseases
O-(chloroacetylcarbamoyl)fumagillol
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on September 29, 2014