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

Primary Purpose

Sarcoma, Kaposi, HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Etoposide
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoma, Kaposi focused on measuring Sarcoma, Kaposi, Drug Evaluation, Etoposide, Acquired Immunodeficiency Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • San Francisco Gen Hosp
  • Bellevue Hosp / New York Univ Med Ctr
  • Mem Sloan - Kettering Cancer Ctr
  • Saint Luke's - Roosevelt Hosp Ctr
  • Univ of Rochester Medical Center
  • Julio Arroyo

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 26, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT00000660
Brief Title
Phase I Study of Weekly Oral VP-16 for AIDS-Associated Kaposi's Sarcoma
Official Title
Phase I Study of Weekly Oral VP-16 for AIDS-Associated Kaposi's Sarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 1992 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma, Kaposi, HIV Infections
Keywords
Sarcoma, Kaposi, Drug Evaluation, Etoposide, Acquired Immunodeficiency Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
24 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Etoposide

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J Kahn
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
S Krown
Official's Role
Study Chair
Facility Information:
Facility Name
San Francisco Gen Hosp
City
San Francisco
State/Province
California
ZIP/Postal Code
941102859
Country
United States
Facility Name
Bellevue Hosp / New York Univ Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Mem Sloan - Kettering Cancer Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Saint Luke's - Roosevelt Hosp Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10025
Country
United States
Facility Name
Univ of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Julio Arroyo
City
West Columbia
State/Province
South Carolina
ZIP/Postal Code
29169
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
7749790
Citation
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.
Results Reference
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Phase I Study of Weekly Oral VP-16 for AIDS-Associated Kaposi's Sarcoma

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