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
  Purpose

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.


Condition Intervention Phase
Sarcoma, Kaposi
HIV Infections
Drug: Etoposide
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Primary Purpose: Treatment
Official Title: Phase I Study of Weekly Oral VP-16 for 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: 24
Study Completion Date: July 1992
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00000660

Locations
United States, California
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
United States, New York
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
Saint Luke's - Roosevelt Hosp Ctr
New York, New York, United States, 10025
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Chair: J Kahn
Study Chair: S Krown
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000660     History of Changes
Other Study ID Numbers: ACTG 110, 11085
Study First Received: November 2, 1999
Last Updated: March 28, 2012
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
AIDS-Related Opportunistic Infections
HIV Infections
Sarcoma
Sarcoma, Kaposi
DNA Virus Infections
Herpesviridae Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Infection
Lentivirus Infections
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neoplasms, Vascular Tissue
Opportunistic Infections
Parasitic Diseases
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Etoposide
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014