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A Phase I Study of TNP-470 in the Treatment of AIDS-Associated Kaposi's Sarcoma
This study has been completed.
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000763
  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 I

MedlinePlus related topics: AIDS Cancer Kaposi's Sarcoma Soft Tissue Sarcoma
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Dose Comparison, Pharmacokinetics Study
Official Title: A Phase I Study of TNP-470 in the Treatment of AIDS-Associated Kaposi's Sarcoma

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

Estimated Enrollment: 42
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000763

Locations
United States, California
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
K Norris Cancer Hosp / Los Angeles County - USC Med Ctr
Los Angeles, California, United States, 900331079
United States, Illinois
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
United States, Massachusetts
Beth Israel Deaconess Med Ctr
Boston, Massachusetts, United States, 02215
Boston Med Ctr
Boston, Massachusetts, United States, 02118
United States, New York
SUNY / State Univ of New York
Syracuse, New York, United States, 13210
Mount Sinai Med Ctr
New York, New York, United States, 10029
Beth Israel Med Ctr
New York, New York, United States, 10003
Albany Med College / Division of HIV Medicine A158
Albany, New York, United States, 122083479
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
Sponsors and Collaborators
Investigators
Study Chair: Gill PS
Study Chair: Dezube B
  More Information

Publications:
Study ID Numbers: ACTG 215
Study First Received: November 2, 1999
Last Updated: June 23, 2005
ClinicalTrials.gov Identifier: NCT00000763  
Health Authority: United States: Federal Government

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

Study placed in the following topic categories:
Sexually Transmitted Diseases, Viral
Malignant mesenchymal tumor
Acquired Immunodeficiency Syndrome
Sarcoma, Kaposi
O-(chloroacetylcarbamoyl)fumagillol
Soft tissue sarcomas
Immunologic Deficiency Syndromes
Herpesviridae Infections
Virus Diseases
Neoplasms, Connective and Soft Tissue
Kaposi sarcoma
HIV Infections
Sexually Transmitted Diseases
Sarcoma
DNA Virus Infections
Retroviridae Infections

Additional relevant MeSH terms:
RNA Virus Infections
Slow Virus Diseases
Neoplasms by Histologic Type
Immune System Diseases
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Infection
Antibiotics, Antineoplastic
Angiogenesis Inhibitors
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Lentivirus Infections
Neoplasms, Vascular Tissue
Growth Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on January 15, 2009