A Randomized Comparison of Three Regimens of Chemotherapy With Compatible Antiretroviral Therapy for Treatment of Advanced AIDS-KS in Resource-Limited Settings
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 334
- 试验地点
- 11
- 主要终点
- Cumulative Rate of Progression-Free Survival by Week 48 for ET+ART vs. PTX+ART
研究概览
简要总结
This study was done to compare the safety and efficacy of three combination treatments for Kaposi's Sarcoma (KS) and AIDS:
- Etoposide (ET) plus co-formulated Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) (ET+ART),
- Bleomycin and Vincristine (BV) plus co-formulated EFV/FTC/TDF (BV+ART),
- Paclitaxel (PTX) plus co-formulated EFV/FTC/TDF (PTX+ART).
详细描述
The study consisted of four steps. Study duration was up to 240 weeks.
At the study Step 1 entry, participants were randomized with equal probability to each of the three regimens (ET+ART, BV+ART, PTX+ART). The original target sample size was 706. Randomization was stratified by:
- Screening CD4 lymphocyte cell count (<100, >=100 cells/mm³), and
- Country.
For participants who had an initial Independent Endpoint Review Committee (IERC) confirmed KS response and subsequent IERC-confirmed KS progression, and who, in the opinion of the investigator and with concurrence of the protocol Clinical Management Committee (CMC), could potentially have benefitted from another course of the same chemotherapy utilized in Step 1, entered Step 2. (Please see details on Step 2 eligibility.)
In Step 3, participants were randomized with equal probability to one of the two chemotherapy arms not utilized in Step 1. (Please see details on Step 3 eligibility.)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
ET+ART
Etoposide (ET) plus co-formulated Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF)
干预措施: Etoposide (ET) (Drug)
ET+ART
Etoposide (ET) plus co-formulated Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF)
干预措施: Co-formulated Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) (Drug)
BV+ART
Bleomycin and Vincristine (BV) plus co-formulated Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF)
干预措施: Bleomycin and Vincristine (BV) (Drug)
BV+ART
Bleomycin and Vincristine (BV) plus co-formulated Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF)
干预措施: Co-formulated Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) (Drug)
PTX+ART
Paclitaxel (PTX) plus co-formulated Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF)
干预措施: Paclitaxel (PTX) (Drug)
PTX+ART
Paclitaxel (PTX) plus co-formulated Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF)
干预措施: Co-formulated Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) (Drug)
结局指标
主要结局
Cumulative Rate of Progression-Free Survival by Week 48 for ET+ART vs. PTX+ART
时间窗: From study entry to week 48
Progression-free survival (PFS) by week 48 is defined as a lack of the following events: (a) Independent Endpoint Review Committee (IERC)-confirmed KS progression, (b) death, (c) entry into an additional step, or (d) loss to follow-up, prior to week 48. PFS rate was estimated by the Kaplan-Meier survival probability at week 48. Time to event was computed as the number of weeks from study entry to the first among these events. For participants who did not have any of the events, event time was censored at the week of last contact with the participant. Follow-up time beyond 48 was censored at week 48. Overall KS outcome status (complete response, partial response, stable, disease progression) was based on comparing follow-up to study entry or best KS response with respect to clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).
Cumulative Rate of Progression-Free Survival by Week 48 for BV+ART vs. PTX+ART
时间窗: From study entry to week 48
Progression-free survival (PFS) by week 48 is defined as a lack of the following events: (a) Independent Endpoint Review Committee (IERC)-confirmed KS progression, (b) death, (c) entry into an additional step, or (d) loss to follow-up, prior to week 48. PFS rate was estimated by the Kaplan-Meier survival probability at week 48. Time to event was computed as the number of weeks from study entry to the first among these events. For participants who did not have any of the events, event time was censored at the week of last contact with the participant. Follow-up time beyond 48 was censored at week 48. Overall KS outcome status (complete response, partial response, stable, disease progression) was based on comparing follow-up to study entry or best KS response with respect to clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).
次要结局
- Cumulative Rate of IERC-confirmed KS Progression by Week 48 for BV+ART vs. PTX+ART(From study entry to week 48)
- Cumulative Rate of Death by Week 48 for ET+ART vs. PTX+ART(From study entry to week 48)
- Cumulative Rate of Death by Week 48 for BV+ART vs. PTX+ART(From study entry to week 48)
- Cumulative Rate of IERC-confirmed KS Progression by Week 48 for ET+ART vs. PTX+ART(From study entry to week 48)
- Cumulative Rate of KS Progression, Death, AIDS Defining Event, or Virologic Failure by Week 48 for ET+ART vs. PTX+ART(From study entry to week 48)
- Number of Participants With Objective Response for ET+ART vs. PTX+ART(From study entry up to week 144)
- Number of Participants With IERC-Confirmed KS Disease Progression, Dose-Limiting Toxicity, Death, AIDS-Defining Events, Virologic Failure and Objective Response in Step 4(From Step 4 study entry to Step 4 discontinuation, up to 96 weeks)
- Cumulative Rate of Death for ET+ART vs. PTX+ART(From study entry to week 240)
- Changes in CD4+ Lymphocyte Cell Count for BV+ART vs. PTX+ART(Baseline, weeks 12, 24, 48)
- Cumulative Rate of AIDS-defining Event by Week 48 for ET+ART vs. PTX+ART(From study entry to week 48)
- Cumulative Rate of AIDS-defining Event by Week 48 for BV+ART vs. PTX+ART(From study entry to week 48)
- Cumulative Rate of HIV-1 RNA Virologic Failure by Week 48 for ET+ART vs. PTX+ART(From study entry to week 48)
- Cumulative Rate of HIV-1 RNA Virologic Failure by Week 48 for BV+ART vs. PTX+ART(From study entry to week 48)
- Number of Participants With Kaposi's Sarcoma-Immune Reconstitution Inflammatory Syndrome (KS-IRIS) for BV+ART vs. PTX+ART(From study entry to week 12)
- Cumulative Rate of KS Progression, Death, or AIDS Defining Event by Week 48 for BV+ART vs. PTX+ART(From study entry to week 48)
- Cumulative Rate of KS Progression, Death, AIDS Defining Event, or Virologic Failure by Week 48 for BV+ART vs. PTX+ART(From study entry to week 48)
- Cumulative Rate of KS Progression, Death, AIDS Defining Event, Virologic Failure, or KS-IRIS by Week 48 for ET+ART vs. PTX+ART(From study entry to week 48)
- Cumulative Rate of KS Progression, Death, AIDS Defining Event, Virologic Failure, or KS-IRIS by Week 48 for BV+ART vs. PTX+ART(From study entry to week 48)
- Number of Participants With Kaposi's Sarcoma-Immune Reconstitution Inflammatory Syndrome (KS-IRIS) for ET+ART vs. PTX+ART(From study entry to week 12)
- Cumulative Rate of Change in KS Treatment by Week 48 for ET+ART vs. PTX+ART(From study entry to week 48)
- Time to IERC-confirmed KS Progression or Death for BV+ART vs. PTX+ART(From study entry to week 240)
- Duration of Objective Response for ET+ART vs. PTX+ART(From study entry up to week 144)
- Number of Participants With Peripheral Neuropathy (PN)(Screening, Weeks 3, 6, 9, 12, 15, 18, 21. Assessment of PN for ET+ART was only done at screening, weeks 9 and 21.)
- Presence of Oral KS(From study entry to week 240)
- Cumulative Rate of KS Progression, Death, or AIDS Defining Event by Week 48 for ET+ART vs. PTX+ART(From study entry to week 48)
- Self-reported Adherence to ART Therapy(At Weeks 6, 12, 18, 30 and 48)
- Number of Participants With IERC-Confirmed KS Disease Progression, Dose-Limiting Toxicity, Death, AIDS-Defining Events, Virologic Failure and Objective Response in Step 2(From Step 2 study entry to Step 2 discontinuation, up to 144 weeks)
- Cumulative Rate of Change in KS Treatment by Week 48 for BV+ART vs. PTX+ART(From study entry to week 48)
- Cumulative Rate of Death for BV+ART vs PTX+ART(From study entry to week 240)
- Time to IERC-confirmed KS Progression or Death for ET+ART vs. PTX+ART(From study entry to week 240)
- Number of Participants With Objective Response for BV+ART vs. PTX+ART(From study entry up to week 144)
- Duration of Objective Response for BV+ART vs. PTX+ART(From study entry up to week 144)
- Number of Participants With Symptomatic Peripheral Neuropathy (SPN)(Screening, Weeks 3, 6, 9, 12, 15, 18, 21. Assessment of SPN for ET+ART was only done at screening, weeks 9 and 21.)
- Number of Participants With Treatment-related Toxicities and Adverse Events (AEs)(From study entry to week 240)
- Changes in CD4+ Lymphocyte Cell Count for ET+ART vs. PTX+ART(Baseline, weeks 12, 24, 48)
- Salivary KSHV(Baseline, weeks 60, 120, 180, 240)
- Number of Participants With IERC-Confirmed KS Disease Progression, Dose-Limiting Toxicity, Death, AIDS-Defining Events, Virologic Failure and Objective Response in Step 3(From Step 3 study entry to Step 3 discontinuation, up to 144 weeks)