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

• Status: Completed
• Trial end date: 1992-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Bristol-Myers Squibb
• Treatments: Etoposide; Etoposide phosphate

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.