Phase I Study of Weekly Oral VP-16 for AIDS-Associated Kaposi's Sarcoma

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000660
First received: November 2, 1999
Last updated: March 28, 2012
Last verified: March 2012

November 2, 1999
March 28, 2012
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Complete list of historical versions of study NCT00000660 on ClinicalTrials.gov Archive Site
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Phase I Study of Weekly Oral VP-16 for AIDS-Associated Kaposi's Sarcoma
Phase I Study of Weekly Oral VP-16 for AIDS-Associated Kaposi's Sarcoma

To define the toxicity and maximum-tolerated dose of weekly oral etoposide (VP-16) in patients with AIDS-related Kaposi's sarcoma; to determine the clinical pharmacology of orally administered VP-16 in AIDS patients. A secondary objective is to obtain preliminary data for determining the effect of oral VP-16 on Kaposi's sarcoma.

VP-16 is an antitumor agent. Previous problems with VP-16 include the route of administration and the toxicities. VP-16 has been given intravenously for 3 consecutive days in a 21-day cycle for lung cancer and testicular cancer. VP-16 has also been used in lymphoma therapy. Oral VP-16 would eliminate the need for an intravenous catheter and so a patient could avoid the pain, inconvenience, and potential complications associated with medications administered intravenously. The relative ease of outpatient administration and the potentially significant antitumor activity of oral VP-16 motivates this study. The possibility of weekly drug administration is the other focus of this study.

VP-16 is an antitumor agent. Previous problems with VP-16 include the route of administration and the toxicities. VP-16 has been given intravenously for 3 consecutive days in a 21-day cycle for lung cancer and testicular cancer. VP-16 has also been used in lymphoma therapy. Oral VP-16 would eliminate the need for an intravenous catheter and so a patient could avoid the pain, inconvenience, and potential complications associated with medications administered intravenously. The relative ease of outpatient administration and the potentially significant antitumor activity of oral VP-16 motivates this study. The possibility of weekly drug administration is the other focus of this study.

Four patients are entered at each dose level starting with level 1. Patients are not entered into the next higher dose level until at least two patients at the previous dose level have completed at least 3 weeks of therapy with grade 2 or less maximum tolerated dose-defining toxicities. Treatment is repeated weekly for 52 weeks until either a grade 3 or 4 toxicity occurs, or until a patient shows a complete response or progressive disease. Patients with a complete response are continued on drug for 4 additional weeks from the time that complete response is first documented. Patients with progressive disease are withdrawn from study. Patients with partial response or stable disease continue until either unacceptable toxicity occurs or a complete response or progression of disease is reached.

Interventional
Phase 1
Endpoint Classification: Pharmacokinetics Study
Primary Purpose: Treatment
  • Sarcoma, Kaposi
  • HIV Infections
Drug: Etoposide
Not Provided
Paredes J, Kahn JO, Tong WP, Feldstein ML, Lin S, Bennett JM, Metroka CE, Ratner L, Krown SE. Weekly oral etoposide in patients with Kaposi's sarcoma associated with human immunodeficiency virus infection: a phase I multicenter trial of the AIDS Clinical Trials Group. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Jun 1;9(2):138-44.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
July 1992
Not Provided

Inclusion Criteria

Concurrent Medication:

AMENDED:

  • 04-21-91 Zidovudine (AZT) allowed after completing 8 weeks on the study. Patients on reduced doses of VP-16 must have tolerated at least 4 consecutive weeks at the reduced dose before starting AZT. Zidovudine will not be provided by the NIAID Clinical Product Research Repository.

AMENDED:

  • Zidovudine (AZT) allowed after completing 12 weeks on study.

Allowed:

  • Aerosolized pentamidine for Pneumocystis carinii pneumonia prophylaxis (PCP).

Concurrent Treatment:

Allowed:

  • Local radiotherapy or laser therapy to cosmetically apparent, non-indicator lesions provided the dose to any one lesion does not exceed 300 rads and the total surface area of all lesions treated does not exceed 10 cm2.

Risk Behavior:

Allowed:

  • All risk groups.

Patients must:

  • Have AIDS-related Kaposi's sarcoma.
  • Be ineligible for protocols of higher priority at study center.
  • Be willing to sign an informed consent or have guardian willing to sign.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Active opportunistic infection not specifically allowed.
  • Concurrent neoplasm not specifically allowed.
  • Significant neurologic, cardiac, or liver disease.

Concurrent Medication:

Excluded:

  • Therapy with potentially myelosuppressive, hepatotoxic, or nephrotoxic drugs for an opportunistic infection.

Patients with the following are excluded:

  • Active opportunistic infection not specifically allowed.
  • Ongoing therapy, including maintenance therapy, for an opportunistic infection with potentially myelosuppressive, hepatotoxic, or nephrotoxic drugs.
  • Concurrent neoplasm not specifically allowed.
  • Significant neurologic, cardiac, or liver disease.

Prior Medication:

Excluded:

  • Biologic response modifiers or corticosteroids within 14 days prior to study entry.
  • Cytotoxic chemotherapy within 30 days prior to study entry.
  • Ribavirin within 6 weeks prior to study entry.
  • Azidothymidine (AZT), alpha-interferon, didanosine (ddI), ganciclovir (DHPG), or any other antiretroviral drugs within 1 week prior to study entry.

Prior Treatment:

Excluded within 30 days prior to study entry:

  • Radiation therapy with > 4000 rads.
  • Total skin electron beam therapy.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00000660
ACTG 110, 11085
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Bristol-Myers Squibb
Study Chair: J Kahn
Study Chair: S Krown
National Institute of Allergy and Infectious Diseases (NIAID)
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP