AzTrials
AzTrials

HIV-1 InfectionPhase 3REACT-KSNCT01352117

Antiretroviral Therapy (ART) Alone or With Delayed Chemo Versus ART With Immediate Chemo for Limited AIDS-related Kaposi's Sarcoma

A Phase 3 study testing efavirenz/emtricitabine/tenofovir disoproxil fumarate and etoposide in people with HIV-1 Infection and Kaposi's Sarcoma, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 8 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV-1 Infection, Kaposi's Sarcoma
What is being tested?
efavirenz/emtricitabine/tenofovir disoproxil fumarate and etoposide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
192 participants
Where
8 sitesin 6 countries
Study dates
18 Nov 2011to 29 Nov 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Step 1: Inclusion Criteria

  1. HIV-1 infection.
  2. Biopsy diagnostic of KS at any time prior to study entry.
  3. Limited stage KS defined as stage T0 and some presentations of stage T1. Stage T0 was confined to skin and/or lymph nodes and/or minimal oral disease defined as non-nodular KS confined to the palate. The following presentations of stage T1 KS were also eligible at the discretion of the site investigator:
  • Tumor-associated edema limited to the area(s) of KS without significant functional impairment.
  • Oral KS that consists of flat (non-nodular and non-ulcerating) lesions confined to the soft palate, hard palate, gums, and buccal mucosa.
  • Asymptomatic gastrointestinal KS (i.e., no unexplained abdominal pain or gastrointestinal bleeding).
  1. A minimum of 5 cutaneous marker lesions
  2. Certain laboratory values obtained within 14 days prior to study entry.
  3. For female participants of reproductive potential, a negative serum or urine pregnancy test performed within 7 days prior to study entry.
  4. All participants must have agreed not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization).
  5. Participants who are participating in sexual activity that could lead to pregnancy must have agreed to use a combination of TWO of the following methods- Condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, IUD, tubal ligation, and/or hormone-based contraception. For Etoposide, confirmation of lack of reproductive potential was required for all participants. More information on this criterion can be found in the study protocol.
  6. Ability to swallow oral medications.
  7. Karnofsky performance score >= 60 within 30 days prior to entry.
  8. Ability and willingness of participant or legal guardian/representative to provide informed consent.
  9. Peripheral blood CD4+ lymphocyte cell count obtained within 30 days prior to study entry at a DAIDS-approved laboratory.
  10. For treatment-experienced patients, the availability of an ART regimen that includes at least two ART drugs that in the opinion of the site investigator are expected to have activity based on historical genotypic testing (if available) and treatment history.
  11. For participants who were to receive ART other than EFV/TDF/FTC, the availability of those ART components.

Step 2: Inclusion Criteria

  1. KS progression compared to study entry or best response with ART alone while on Step 1, between weeks 8 and 80.
  2. Need for ET for treatment of KS progression, in the opinion of the site investigator, after confirmation of KS progression by the IERC.
  3. Willingness to receive ET for treatment of KS progression.
  4. For female participants of reproductive potential, a negative serum or urine pregnancy test performed within 7 days prior to initiating ET.
  5. Karnofsky Performance Score >= 50.
  6. Certain laboratory values obtained within 14 days prior to Step 2 entry.
  7. Ability to swallow oral medications.
  8. All participants must have agreed not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization).
  9. Participants who are participating in sexual activity that could lead to pregnancy must have agreed to use a combination of TWO of the following methods- Condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, IUD, tubal ligation, hormone-based contraception. For Etoposide, confirmation of lack of reproductive potential was required for all participants. More information on this criterion can be found in the study protocol.

Step 3: Inclusion Criteria

  1. Received at least one dose of ET (Arm B participants and Arm A participants who entered Step 2)

Step 1: Exclusion Criteria

  1. Any manifestation of KS which, in the opinion of the site investigator, requires immediate chemotherapy.
  2. More than 14 days of ART after onset of KS within 6 months prior to study entry.
  3. Biopsy proven KS during previous ART.
  4. Breastfeeding.
  5. Allergy/sensitivity to any study drug or its formulations.
  6. Any prior systemic anti-neoplastic treatment for KS (including chemotherapy, biological therapy, immunotherapy or investigational therapy).
  7. Any prior local treatment of cutaneous marker lesions unless there was evidence of a clear-cut progression of the lesion.
  8. Receipt of any investigational therapy within 30 days prior to study entry.
  9. Current or anticipated receipt of any of the prohibited medications indicated in the study protocol.
  10. In the opinion of the site investigator, any psychological or social condition, or addictive disorder that would have precluded compliance with the protocol.
  11. Chronic, acute, or recurrent infections that were serious, in the opinion of the site investigator, for which the participant had not completed at least 14 days of therapy prior to study entry and/or was not clinically stable.

Step 2: Exclusion Criteria

  1. Chronic, acute, or recurrent infections that were serious, in the opinion of the site investigator, for which the participant had not completed at least 14 days of therapy prior to initiating ET and/or was not clinically stable.
  2. Current or anticipated receipt of any of the prohibited medications indicated in the study protocol.
  3. Breastfeeding.

There are no exclusion criteria for Step 3.

Trial locations and contacts

8 sites in 6 countries.

8 sites in 6 countries

Malawi2 sites

  • College of Med. JHU CRS (30301)

    Blantyre

  • University of North Carolina Lilongwe CRS (12001)

    Lilongwe

Other trials in Malawi

South Africa2 sites

  • Durban Adult HIV CRS (11201)

    Durban, 4013 SF

  • Wits HIV CRS

    Johannesburg, Gauteng

Other trials in South Africa

Brazil1 site

  • Instituto de Pesquisa Clinica Evandro Chagas (12101)

    Rio de Janeiro, 21045

Other trials in Brazil

Kenya1 site

  • Walter Reed Project - Kenya Med. Research Institute Kericho CRS (12501)

    Kericho, 20200

Other trials in Kenya

Peru1 site

  • San Miguel CRS

    San Miguel, Lima region

Other trials in Peru

Uganda1 site

  • JCRC CRS

    Kampala

Other trials in Uganda

About this study

Official title: 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

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.

Read the detailed description

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:

  1. Screening CD4 cell count (<200 or ≥200 cells/mm^3) and
  2. 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.

Being tested
efavirenz/emtricitabine/tenofovir disoproxil fumarate, etoposide
Medical subject headings
Sarcoma, Kaposi

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • efavirenz/emtricitabine/tenofovir disoproxil fumarateDrug

    Also called Atripla®, EFV/FTC/TDF

    600 mg efavirenz/200 mg emtricitabine/300 mg tenofovir disoproxil fumarate taken orally at night

  • etoposideDrug

    Also called VePesid®, ET

    50 mg taken orally daily from days 1-7 of each 2-week cycle. For participants without PR or CR after two cycles of therapy and no toxicity greater than Grade 2, the dose of ET was escalated to 100 mg/day orally, days 1-7, every 2 weeks. A cycle could be delayed for a maximum of 14 days. ET could not be initiated prior to 7 days after the last dose in previous cycle. ET could be administered up to a maximum of eight cycles (2 cycles during dose titration and 6 cycles at maximum dose). Participants who could not tolerate escalation of the ET dose to 100 mg/day were treated for a maximum of six cycles.

Study groups in NCT01352117
Study groupRoleWhat they receive
Arm A: ART alone or with delayed ETActive comparatorParticipants 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.
Receives: Drug: efavirenz/emtricitabine/tenofovir disoproxil fumarate; Drug: etoposide
Arm B: ART with immediate ETExperimentalParticipants were prescribed ART (co-formulated efavirenz/emtricitabine/tenofovir disoproxil fumarate, EFV/FTC/TDF) for 96 weeks with immediate ET for up to 16 weeks.
Receives: Drug: efavirenz/emtricitabine/tenofovir disoproxil fumarate; Drug: etoposide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Kaposi Sarcoma (KS) Status at Week 48 Compared to Study Entry

    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

    Measured: Entry through Week 48.

Secondary outcomes (24)

  1. KS Progressive Disease at Week 48 Compared to Study Entry

    KS progressive disease (PD) compared to study entry 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).

    Measured: Entry and Week 48

  2. KS Partial Response at Week 48 Compared to Study Entry

    KS partial response (PR) compared to study entry 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).

    Measured: Entry and Week 48

  3. KS Complete Response at Week 48 Compared to Study Entry

    KS complete response (CR) compared to study entry 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).

    Measured: Entry and Week 48

  4. KS Partial or Complete Response at Week 48 Compared to Study Entry

    KS partial response (PR) or complete response (CR) compared to study entry 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).

    Measured: Entry and Week 48

  5. Premature Study Discontinuation by Week 48

    Premature study discontinuation by Week 48 due to any reason, including death.

    Measured: Entry through Week 48

  6. Kaposi Sarcoma (KS) Status at Week 96 Compared to Study Entry

    KS status is a composite, categorical outcome, ordered from worst to best as E1 (Failure: KS PD, initiation of an alternate KS treatment, or no follow-up at Week 96 including death and missed visit), E2 (Stable: in follow-up at Week 96 with no KS progression nor response and without initiation of an alternate KS treatment) and E3 (Response: in follow-up at Week 96, with KS 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 (PD, stable, PR or CR) compared to study entry was evaluated at Week 96 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 deaths are from entry through Week 96.

    Measured: Entry through Week 96.

  7. KS Progressive Disease at Week 96 Compared to Study Entry

    KS progressive disease (PD) compared to study entry 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).

    Measured: Entry and Week 96

  8. KS Partial Response at Week 96 Compared to Study Entry

    KS partial response (PR) compared to study entry 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).

    Measured: Entry and Week 96

  9. KS Complete Response at Week 96 Compared to Study Entry

    KS complete response (CR) compared to study entry 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).

    Measured: Entry and Week 96

  10. KS Partial or Complete Response at Week 96 Compared to Study Entry

    KS partial response (PR) or complete response (CR) compared to study entry 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).

    Measured: Entry and Week 96

  11. Premature Study Discontinuation by Week 96

    Premature study discontinuation by Week 96 due to any reason, including death.

    Measured: Entry through Week 96

  12. Cumulative Incidence of Initial KS Progressive Disease by Week 96

    KS progressive disease (PD) compared to study entry or best response 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). Cumulative incidence was estimated with death and initiation of alternate KS treatment as competing risks. Time at risk was censored at the end of Step 1 (Week 96 or premature study discontinuation) or on the date when the DSMB's recommendation to close the study became public, whichever occurred earlier.

    Measured: From entry through 96 weeks

  13. Cumulative Incidence of Initial KS Partial or Complete Response by Week 96

    KS partial response (PR) or complete response (CR) compared to study entry 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). Cumulative incidence was estimated with death and initiation of delayed KS treatment (alternate KS treatment or delayed ET in Arm A) as competing risks. Time at risk was censored at the end of Step 1 (Week 96 or premature study discontinuation) or on the date when the DSMB's recommendation to close the study became public, whichever occurred earlier.

    Measured: From entry through 96 weeks

  14. Cumulative Incidence of Initial KS Partial Response by Week 96

    KS partial response (PR) compared to study entry 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). This was initially part of the outcome specified in the study protocol as "PR and CR combined and separately" to address the secondary objective on the KS response. Due to the extremely limited number of participants with KS complete response, the Statistical Analysis Plan was updated, and the Final Analysis was conducted only on the combined KS response. The outcome on PR separately was withdrawn.

    Measured: From study treatment initiation to 96 weeks

  15. Cumulative Incidence of Initial KS Complete Response by Week 96

    KS complete response (CR) compared to study entry based on clinical evaluation 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). This was initially part of the outcome specified in the study protocol as "PR and CR combined and separately" to address the secondary objective on the KS response. Due to the extremely limited number of participants with KS CR, the Statistical Analysis Plan was updated, and the Final Analysis was conducted only on the combined KS response. The outcome on CR separately was withdrawn.

    Measured: From study treatment initiation to 96 weeks

  16. Number of Participants With Grade 3 or Higher Adverse Events

    Number of participants who experienced an AE (sign/symptom or laboratory abnormality) of Grade 3 or higher. The AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see reference in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening.

    Measured: From study treatment dispensation through up to Week 96, until long-term follow-up began in Step 3 or until study discontinuation.

  17. Cumulative Incidence of KS-IRIS

    KS-IRIS was defined as KS progressive disease that occurs within 12 weeks of initiation of ART that is associated with an increase in peripheral blood CD4+ lymphocyte cell count of at least 50 cells/mm^3 above the study screening value and/or a decrease in the HIV RNA level by at least 0.5 log10 below the study entry value prior to, or at the time of, documented KS progressive disease. Cumulative incidence was estimated with death and initiation of alternate KS treatment as competing risks. Time at risk was censored (1) when lost to follow-up, (2) at the study visit following Week 12 or (3) on the date when the DSMB's recommendation to close the study became public, whichever occurred earlier. Time of KS-IRIS was defined as the time of the initial KS progressive disease.

    Measured: From study entry to Week 12

  18. Percentage of Participants With Etoposide Dose Modification

    Etoposide (ET) was administered for a maximum of 8 cycles (16 weeks) from study entry (Arm B) or from Step 2 entry (Arm A). Dose modifications were reported as temporarily held, resumed at a different dose, deferred, prematurely discontinued and underdosed. The percentage of participants who experienced each dose modification is provided in the data table below. The categories are not mutually exclusive. A participant may have experienced multiple dose modifications and may be counted in more than one category. Each participant is counted at most once within category.

    Measured: From ET dispensation to ET discontinuation (total duration of ET was up to 16 weeks)

  19. Percentage of Participants With HIV-1 RNA Suppression

    HIV-1 RNA suppression was defined as plasma HIV-1 RNA <400 copies/mL. Only Arm A participants could enter Step 2 to initiate delayed ET.

    Measured: Entry and Weeks 12, 24, 32, 48, 72, 96; Step 2 entry and Weeks 12, 24, 32, 48 and 72.

  20. Percentage of Participants With ARV Dose Modification

    ARV dose modifications were reported as temporarily held, prematurely discontinued and increased. The percentage of participants who experienced each dose modification is provided in the data table below. The categories are not mutually exclusive. A participant may have experienced multiple dose modifications and may be counted in more than one category. Each participant is counted at most once within category.

    Measured: From treatment dispensation to Week 96

  21. Change in log10 HIV-1 Plasma Viral Load From Entry

    Absolute change in log10 HIV-1 RNA from entry at study visits calculated as value at a given time point minus value at entry. This outcome was initially specified in the study protocol. However, at the first post-entry visit, most participants had unquantifiable HIV-1 RNA levels. It would be misleading to calculate change from entry to HIV RNA-1 levels that could not be quantified. Therefore, the data collected did not support the outcome and the analytic method initially proposed in the study protocol, and this outcome measure could not be analyzed. The SAP updated the HIV-1 RNA outcome measure to HIV-1 RNA suppression at study visits (please refer to the secondary outcome measure #20).

    Measured: Entry and Weeks 12, 24, 32, 48, 72, 96; Step 2 entry and Weeks 12, 24, 32, 48 and 72.

  22. Change in Peripheral Blood CD4+ Lymphocyte Cell Count

    Absolute change in CD4+ cell count was calculated as value at a given visit minus the value at study screening in Step 1, and as value at a given visit minus Step 2 entry in Step 2. Only participants in Arm A could enter Step 2 to initiate delayed ET.

    Measured: Screening and Weeks 12, 24, 32, 48, 72, 96; Step 2 entry and Weeks 12, 24, 32, 48 and 72.

  23. Cumulative Incidence of KS Progressive Disease After Initiation of Delayed Etoposide in Arm A

    KS progressive disease (PD) compared to Step 2 entry (prior to initiation of delayed ET) or Step 2 best response 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). Cumulative incidence was estimated with death and initiation of alternate KS treatment as competing risks. Time at risk was censored at the end of Step 2 (at up to 84 weeks or premature study discontinuation) or on the date when the DSMB's recommendation to close the study became public, whichever occurred earlier.

    Measured: From initiation of etoposide (Step 2 entry) to up to 84 weeks (end of Step 2)

  24. Cumulative Incidence of KS Response After Initiation of Delayed Etoposide in Arm A

    KS response, partial or complete (PR or CR) compared to Step 2 entry (prior to initiation of delayed ET) 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). Cumulative incidence was estimated with death and initiation of alternate KS treatment as competing risks. Time at risk was censored at the end of Step 2 (at up to 84 weeks or premature study discontinuation) or on the date when the DSMB's recommendation to close the study became public, whichever occurred earlier.

    Measured: From initiation of etoposide (Step 2 entry) to up to 84 weeks (end of Step 2)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 May 2011 (estimated)
  2. Study start18 Nov 2011
  3. Primary completion16 Mar 2016
  4. Study completion29 Nov 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
192 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01352117
Sponsor's protocol ID
ACTG A5264
Other IDs
1U01AI068636, AMC 067
Acronym
REACT-KS
Status last verified
Nov 2019
First submitted
3 Mar 2011
Last updated
14 Nov 2019
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009).

  • Manual for Expedited Reporting of Adverse Events to DAID, Version 2.0, January 2010. http://rsc.tech-res.com/clinical-research-sites/safety-reporting/manual

  • Krown SE, Metroka C, Wernz JC. Kaposi's sarcoma in the acquired immune deficiency syndrome: a proposal for uniform evaluation, response, and staging criteria. AIDS Clinical Trials Group Oncology Committee. J Clin Oncol. 1989 Sep;7(9):1201-7. doi: 10.1200/JCO.1989.7.9.1201.

    PubMed 2671281

  • Cianfrocca M, Cooley TP, Lee JY, Rudek MA, Scadden DT, Ratner L, Pluda JM, Figg WD, Krown SE, Dezube BJ. Matrix metalloproteinase inhibitor COL-3 in the treatment of AIDS-related Kaposi's sarcoma: a phase I AIDS malignancy consortium study. J Clin Oncol. 2002 Jan 1;20(1):153-9. doi: 10.1200/JCO.2002.20.1.153.

    PubMed 11773164

  • Hosseinipour MC, Kang M, Krown SE, Bukuru A, Umbleja T, Martin JN, Orem J, Godfrey C, Hoagland B, Mwelase N, Langat D, Nyirenda M, MacRae J, Borok M, Samaneka W, Moses A, Mngqbisa R, Busakhala N, Martinez-Maza O, Ambinder R, Dittmer DP, Nokta M, Campbell TB; A5264/AMC-067 REACT-KS Team. As-Needed Vs Immediate Etoposide Chemotherapy in Combination With Antiretroviral Therapy for Mild-to-Moderate AIDS-Associated Kaposi Sarcoma in Resource-Limited Settings: A5264/AMC-067 Randomized Clinical Trial. Clin Infect Dis. 2018 Jul 2;67(2):251-260. doi: 10.1093/cid/ciy044.

    PubMed 29365083

  • Epeldegui M, Chang D, Lee J, Magpantay LI, Borok M, Bukuru A, Busakhala N, Godfrey C, Hosseinipour MC, Kang M, Kanyama C, Langat D, Mngqibisa R, Mwelase N, Nyirenda M, Samaneka W, Hoagland B, Campbell TB, Martinez-Maza O, Krown SE; A5264/AMC-067 team. Predictive Value of Serum Biomarkers for Response of Limited-Stage AIDS-Associated Kaposi Sarcoma to Antiretroviral Therapy With or Without Concomitant Chemotherapy in Resource-Limited Settings. J Acquir Immune Defic Syndr. 2023 Oct 1;94(2):165-173. doi: 10.1097/QAI.0000000000003236.

    PubMed 37368929

  • Kang M, Grund B, Hunsberger S, Glidden D, Volberding P. Interim monitoring in a treatment strategy trial with a composite primary endpoint. Contemp Clin Trials. 2019 Nov;86:105846. doi: 10.1016/j.cct.2019.105846. Epub 2019 Sep 11.

    PubMed 31520741

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing efavirenz/emtricitabine/tenofovir disoproxil fumarate and etoposide in people with HIV-1 Infection and Kaposi's Sarcoma, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 8 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Malawi, South Africa, Brazil, Kenya, Peru and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Kaposi Sarcoma (KS) Status at Week 48 Compared to Study Entry (time frame: Entry through Week 48.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01352117, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2019.

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REACT-KS Clinical Trial NCT01352117 | AzTrials