A Randomized Evaluation of Antiretroviral Therapy Alone or With Delayed Chemotherapy Versus Antiretroviral Therapy With Immediate Adjunctive Chemotherapy for Treatment of Limited Stage AIDS-KS in Resource-Limited Settings (REACT-KS) AMC 067
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 192
- 试验地点
- 8
- 主要终点
- Kaposi Sarcoma (KS) Status at Week 48 Compared to Study Entry
研究概览
简要总结
AIDS-related Kaposi's sarcoma (AIDS-KS) occurs in persons with HIV infection who are also infected with the Kaposi's sarcoma herpesvirus (KSHV). Several chemotherapy (anti-cancer) drugs work well in treating KS, but there is no treatment that cures KSHV infection. One chemotherapy drug called etoposide (VePesid®, ET) has caused KS tumors to get smaller in some people.
Antiretroviral therapy (anti-HIV drugs or ART) is a group of medicines taken together to treat HIV infection. These medicines help to stop HIV from growing in the body. When this happens, the immune system, which fights infection and some cancers like KS, gets stronger. For some people, limited stage KS often improves or stays the same when they take ART. However, in some people KS continues to get worse when taking ART. These people may need chemotherapy at a later date.
This study was done to find out if taking ART with immediate etoposide (ET) is better than taking ART alone or ART with delayed ET to treat limited stage KS. The study also tried to better understand KSHV and to see what kind of side effects are caused by ART and ET and how safe ART and ET are.
详细描述
The study consisted of three steps. At the study Step 1 entry, the participants were randomized (1:1) to receive ART alone (Arm A) or ART with immediate ET (Arm B). Study participants in Arm A who experienced KS progression that was confirmed by the Independent Endpoint Review Committee (IERC) could receive etoposide (ET) in addition to ART by entering Step 2 between study weeks 8 and 80. The target sample size was 468, 234 per arm. Randomization was stratified by:
- Screening CD4 cell count (<200 or ≥200 cells/mm^3) and
- ART history (naïve or experienced).
The duration of Step 1 or Step 1 and 2 combined was 96 weeks. After 96 weeks on study, participants who received ET (Arm B participants and Arm A participants who entered Step 2) entered Step 3 for a total of 144 weeks of safety follow-up.
Step 1 visits occurred at screening, entry and weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96 from study entry. Step 2 visits were scheduled at entry and weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 32, 40, 48, 60, 72, 84 from Step 2 entry until up to 96 weeks on study. The key evaluations included physical examination, clinical assessments, KS exam, CD4 cell count, HIV viral load, hematology, chemistry and pregnancy testing (for women of reproductive potential). Plasma, serum, peripheral blood mononuclear cells (PBMCs), KS tumor punch biopsy were be stored for use in future analyses. Participants also completed ET and ART adherence evaluations and quality of life questionnaires. Step 3 visits were scheduled every 24 weeks and were limited to safety evaluations including targeted physical exam, clinical assessments and hematology.
Study accrual terminated early, based on the Data and Safety Monitoring Board (DSMB) recommendation in March 2016. The participants in Steps 1 and 2 at that time were arranged to enter either Step 3 for safety follow-up after ET or, if they did not receive ET, to be taken off study.
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
Arm A: ART alone or with delayed ET
Participants were prescribed ART (co-formulated efavirenz/emtricitabine/tenofovir disoproxil fumarate, EFV/FTC/TDF) for 96 weeks. Arm A participants who experienced KS progression on ART alone could receive ET in addition to EFV/FTC/TDF in Step 2 of the study.
干预措施: efavirenz/emtricitabine/tenofovir disoproxil fumarate (Drug)
Arm A: ART alone or with delayed ET
Participants were prescribed ART (co-formulated efavirenz/emtricitabine/tenofovir disoproxil fumarate, EFV/FTC/TDF) for 96 weeks. Arm A participants who experienced KS progression on ART alone could receive ET in addition to EFV/FTC/TDF in Step 2 of the study.
干预措施: etoposide (Drug)
Arm B: ART with immediate ET
Participants were prescribed ART (co-formulated efavirenz/emtricitabine/tenofovir disoproxil fumarate, EFV/FTC/TDF) for 96 weeks with immediate ET for up to 16 weeks.
干预措施: efavirenz/emtricitabine/tenofovir disoproxil fumarate (Drug)
Arm B: ART with immediate ET
Participants were prescribed ART (co-formulated efavirenz/emtricitabine/tenofovir disoproxil fumarate, EFV/FTC/TDF) for 96 weeks with immediate ET for up to 16 weeks.
干预措施: etoposide (Drug)
结局指标
主要结局
Kaposi Sarcoma (KS) Status at Week 48 Compared to Study Entry
时间窗: Entry through Week 48.
KS status is a composite, categorical outcome, ordered from worst to best as E1 (Failure: KS progression (PD), initiation of an alternate KS treatment, or no follow-up at Week 48 including death and missed visit), E2 (Stable: in follow-up at Week 48 with no KS PD nor response and without initiation of an alternate KS treatment) and E3 (Response: in follow-up at Week 48, with KS partial or complete response (PR or CR) and without initiation of an alternate KS treatment). Alternate KS treatment was defined as chemotherapy agent other than ET or other treatment triggered by worsening KS. KS outcome status (PR, stable, PR, CR) compared to study entry was evaluated at Week 48 based on 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). Data on initiation of alternate KS treatment, loss to follow-up and dea
次要结局
- KS Complete Response at Week 48 Compared to Study Entry(Entry and Week 48)
- KS Partial Response at Week 48 Compared to Study Entry(Entry and Week 48)
- Change in log10 HIV-1 Plasma Viral Load From Entry(Entry and Weeks 12, 24, 32, 48, 72, 96; Step 2 entry and Weeks 12, 24, 32, 48 and 72.)
- Change in Peripheral Blood CD4+ Lymphocyte Cell Count(Screening and Weeks 12, 24, 32, 48, 72, 96; Step 2 entry and Weeks 12, 24, 32, 48 and 72.)
- Cumulative Incidence of KS Progressive Disease After Initiation of Delayed Etoposide in Arm A(From initiation of etoposide (Step 2 entry) to up to 84 weeks (end of Step 2))
- Cumulative Incidence of KS Response After Initiation of Delayed Etoposide in Arm A(From initiation of etoposide (Step 2 entry) to up to 84 weeks (end of Step 2))
- KS Progressive Disease at Week 48 Compared to Study Entry(Entry and Week 48)
- KS Partial or Complete Response at Week 48 Compared to Study Entry(Entry and Week 48)
- Premature Study Discontinuation by Week 48(Entry through Week 48)
- KS Complete Response at Week 96 Compared to Study Entry(Entry and Week 96)
- KS Partial Response at Week 96 Compared to Study Entry(Entry and Week 96)
- Kaposi Sarcoma (KS) Status at Week 96 Compared to Study Entry(Entry through Week 96.)
- KS Progressive Disease at Week 96 Compared to Study Entry(Entry and Week 96)
- KS Partial or Complete Response at Week 96 Compared to Study Entry(Entry and Week 96)
- Premature Study Discontinuation by Week 96(Entry through Week 96)
- Cumulative Incidence of Initial KS Progressive Disease by Week 96(From entry through 96 weeks)
- Cumulative Incidence of Initial KS Partial or Complete Response by Week 96(From entry through 96 weeks)
- Cumulative Incidence of Initial KS Partial Response by Week 96(From study treatment initiation to 96 weeks)
- Number of Participants With Grade 3 or Higher Adverse Events(From study treatment dispensation through up to Week 96, until long-term follow-up began in Step 3 or until study discontinuation.)
- Cumulative Incidence of Initial KS Complete Response by Week 96(From study treatment initiation to 96 weeks)
- Cumulative Incidence of KS-IRIS(From study entry to Week 12)
- Percentage of Participants With Etoposide Dose Modification(From ET dispensation to ET discontinuation (total duration of ET was up to 16 weeks))
- Percentage of Participants With HIV-1 RNA Suppression(Entry and Weeks 12, 24, 32, 48, 72, 96; Step 2 entry and Weeks 12, 24, 32, 48 and 72.)
- Percentage of Participants With ARV Dose Modification(From treatment dispensation to Week 96)