Three Chemo Regimens as an Adjunct to ART for Treatment of Advanced AIDS-KS

Summary

This study was done to compare the safety and efficacy of three combination treatments for Kaposi's Sarcoma (KS) and AIDS:

1. Etoposide (ET) plus co-formulated Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) (ET+ART),
2. Bleomycin and Vincristine (BV) plus co-formulated EFV/FTC/TDF (BV+ART),
3. Paclitaxel (PTX) plus co-formulated EFV/FTC/TDF (PTX+ART).

Conditions

• HIV-1 Infection

Interventions

DRUG

Etoposide (ET)

Beginning on day one of the chemotherapy cycle, ET was given orally in a dose of 50 mg twice daily for 7 consecutive days for the first cycle. If there was no Grade \>= 2 toxicity attributable to ET after the first cycle, the dose was escalated to 150 mg daily for 7 days in divided doses of 100 mg/50 mg for the second cycle. After the second cycle, if there was no Grade \>= 2 toxicity attributable to ET, the dose was escalated to 100 mg twice daily for 7 days for the third and subsequent cycles. Treatment with ET was continued for six cycles at the maximum dose achieved or until toxicity requiring discontinuation of study chemotherapy, or the site investigator, after consulting with the protocol CMC, had determined that alternative therapy is required, whichever occurs first.

DRUG

Bleomycin and Vincristine (BV)

BV was administered on day one of each chemotherapy cycle. Vincristine sulfate was administered at a dose of 2 mg (fixed dose) in a volume of 2 mL over 1 minute into the sidearm of a rapidly flowing intravenous infusion every 3 weeks. The vincristine infusion was followed by bleomycin as detailed below. Bleomycin sulfate was administered at a dose of 15 units/m\^2 over 10 minutes every 3 weeks. Treatment with BV was continued for six cycles, or until toxicity requiring discontinuation of study chemotherapy, or the site investigator, after consulting with the protocol CMC, had determined that alternative therapy is required, whichever occurs first.

DRUG

Paclitaxel (PTX)

Paclitaxel was administered by IV infusion in 200 mL, 250 mL, or 500 mL of 5% dextrose or 0.9%Sodium Chloride for injection at a dose of 100 mg/m\^2 body surface area (BSA) every 3 weeks.

DRUG

Co-formulated Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF)

The following ART regimens were used: 1. EFV/FTC/TDF (Atripla) 200 mg/300 mg/600 mg orally once daily at bedtime or 2. FTC/TDF 200 mg/300 mg (Truvada) orally once daily at bedtime plus EFV (Stocrin) 600 mg orally once daily at bedtime or 3. FTC/TDF 200 mg/300 mg (Truvada) orally once daily plus nevirapine (NVP) 200 mg orally twice daily or 4. FTC/TDF 200 mg/300 mg (Truvada) orally once daily plus PI/r at standard dosing or 5. FTC/TDF 200 mg/300 mg (Truvada) orally once daily plus integrase inhibitor at standard dosing

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  collaborator NIH

• National Cancer Institute (NCI)

  collaborator NIH

• National Institute of Dental and Craniofacial Research (NIDCR)

  collaborator NIH

• AIDS Malignancy Consortium

  collaborator NETWORK

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

  lead NETWORK

Principal Investigators

• Margaret Borok-Williams, MD · University of Zimbabwe

• Susan E. Krown, MD · AIDS Malignancy Consortium

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-10-01

Primary Completion

2018-03-13

Completion

2019-08-29

Countries

• Brazil
• Kenya
• Malawi
• South Africa
• Uganda
• Zimbabwe

Study Locations