Pharmacy and Poisons Board
Protocol No: ECCT/24/07/04 Date of Protocol: 14-04-2023
Study Title:

A Phase III, Randomized, Open-Label, Non-Inferiority Study of Paclitaxel and Pegylated Liposomal Doxorubicin for Treatment of HIV-related Kaposi Sarcoma in Resource-Limited Settings

 
Study Objectives:

Primary Objective

To evaluate whether there is sufficient evidence to conclude that PLD is non-inferior to PTX in people with severe AIDS-associated KS receiving concomitant ART in resource-limited settings.

Secondary Objectives

1. To describe the safety and toxicity of PLD and PTX in patients with severe AIDS-KS in resource-limited settings.

2. To estimate the objective response rate (defined as the sum of complete and partial responses) for AIDS-KS, response duration and overall survival in each treatment arm.

Exploratory Objectives

1.  To describe the cost of therapy across AMC sites in sub-Saharan Africa to deliver both PLD and PTX by micro-costing analysis for goods and time-in-motion analysis for services.

2.  To assess quality of life across PROMIS domains (i.e., cognitive function, physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance) with the PROPr tool at start of therapy, mid-treatment, and after treatment with PLD and PTX.

3.  To describe the incremental cost-effectiveness ratio per QALY gained (as assessed by PROPr) between PLD and PTX.

 

 

 
Laymans Summary:

The purpose of this phase III multicenter study is to find out whether Pegylated Liposomal Doxorubicin (PLD) is as effective as Paclitaxel (PTX) in treating people with AIDS associated KS receiving concomitant antiretroviral therapy (ART) in Africa.

 
Abstract of Study:

Title:

A Phase III, Randomized, Open-Label, Non-Inferiority Study of Paclitaxel and Pegylated Liposomal Doxorubicin for Treatment of HIV-related Kaposi Sarcoma in Resource-Limited Settings

Phase of Study:

Phase III

Accrual Target:

Minimum: 118 participants; Maximum: 130 participants

Population:

Participants with HIV-associated Kaposi Sarcoma (KS) in sub-Saharan Africa

Regimen:

Each cycle of treatment includes administration of a single intravenous dose of either paclitaxel (PTX) or pegylated liposomal doxorubicin (PLD) on Day 1 of each 21-day cycle.

Eligible participants will begin study treatment with their randomized study treatment at Dose Level 1: either paclitaxel (PTX) at a dose of 100 mg/m2 or PLD at a dose of 20 mg/m2 on Day 1 of each 21-day cycle, for a total of six treatment cycles.

Dose Level -1 and -2 are provided for participants who require dose reduction.

Safety and the need for dose reduction will be continuously monitored by the protocol team.

Anti-tumor effects will be assessed immediately prior to the start of each 21-day treatment cycle in all participants.

After completion of the prescribed number of treatment cycles, participants will then be followed for safety, anti-tumor effects and survival every 4 weeks until week 48 and then every 12 weeks for a total of 96 weeks.

Anticipated Trial Duration:

4 years (2 years accrual, 2 years follow-up)

Primary Objective:

To evaluate whether there is sufficient evidence to conclude that PLD is non-inferior to PTX in people with severe AIDS-associated KS receiving concomitant antiretroviral therapy (ART) in resource-limited settings.

Secondary Objectives:

1. To describe the safety and toxicity of PLD and PTX in patients with severe AIDS-KS in resource-limited settings.

2. To estimate the objective AIDS-KS response rate (Complete and Partial), response duration and overall survival in each treatment arm.

Exploratory Objectives:

1. To describe the cost of therapy across AMC sites in sub-Saharan Africa to deliver both PLD and PTX by micro-costing analysis for goods and time-in-motion analysis for services.

2. To assess quality of life across PROMIS domains with the PROPr tool at start of therapy, mid-treatment, and after treatment with PLD and PTX. These domains are cognitive function, physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance.

3. To describe the incremental cost-effectiveness ratio per quality-adjusted life years (QALY) gained (as assessed by PROPr) between PLD and PTX.