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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by AIDS Clinical Trials Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01352117
First received: March 3, 2011
Last updated: June 5, 2014
Last verified: June 2014

March 3, 2011
June 5, 2014
October 2011
October 2019   (final data collection date for primary outcome measure)
Number of participants with Kaposi Sarcoma (KS) treatment response at week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
KS treatment response is an ordinal composite measure with three categories defined as: failure (KS progression, initiation of a new chemotherapy agent other than ET, or no follow-up at week 48 including death and missed visit), stable (in follow-up at week 48 with no KS progression nor response and without initiation of a new chemotherapy other than ET) and response (in follow-up at week 48, with KS partial or complete response and without initiation of a new chemotherapy agent other than ET.
Same as current
Complete list of historical versions of study NCT01352117 on ClinicalTrials.gov Archive Site
  • Time from study treatment initiation to initial KS partial response [ Time Frame: From study treatment initiation to 96 weeks ] [ Designated as safety issue: No ]
    Partial response determined by clinician as no new oral lesions, visceral sites of involvement, appearance or worsening of tumor-associated edema or effusions, development of >=5 new cutaneous lesions in sites without cutaneous disease at entry and one or more of: 1) >=50% decrease in number of lesions 2) complete flattening of >=50% of all raised lesions 3) >=50% decrease in the area of the 5 cutaneous marker lesions, compared to entry.
  • Time from study treatment initiation to initial KS complete response [ Time Frame: From study treatment initiation to 96 weeks ] [ Designated as safety issue: No ]
    Complete response determined by clinician as absence of any detectable residual KS disease, including tumor-associated edema.
  • Time from study treatment initiation to initial KS partial or complete response [ Time Frame: From study treatment initiation to 96 weeks ] [ Designated as safety issue: No ]
    Partial response determined by clinician as no new oral lesions, visceral sites of involvement, appearance or worsening of tumor-associated edema or effusions, development of >=5 new cutaneous lesions in sites without cutaneous disease at entry and one or more of: 1) >=50% decrease in number of lesions 2) complete flattening of >=50% of all raised lesions 3) >=50% decrease in the area of the 5 cutaneous marker lesions, compared to entry. Complete response determined by clinician as absence of any detectable residual KS disease, including tumor-associated edema
  • Number of participants with KS partial response [ Time Frame: At weeks 48 and 96 ] [ Designated as safety issue: No ]
    Partial response determined by clinician as no new oral lesions, visceral sites of involvement, appearance or worsening of tumor-associated edema or effusions, development of >=5 new cutaneous lesions in sites without cutaneous disease at entry and one or more of: 1) >=50% decrease in number of lesions 2) complete flattening of >=50% of all raised lesions 3) >=50% decrease in the area of the 5 cutaneous marker lesions, compared to entry.
  • Number of participants with KS complete response [ Time Frame: At weeks 48 and 96 ] [ Designated as safety issue: No ]
    Complete response determined by clinician as absence of any detectable residual KS disease, including tumor-associated edema.
  • Number of participants with KS partial or complete response [ Time Frame: At weeks 48 and 96 ] [ Designated as safety issue: No ]
    Partial response determined by clinician as no new oral lesions, visceral sites of involvement, appearance or worsening of tumor-associated edema or effusions, development of >=5 new cutaneous lesions in sites without cutaneous disease at entry and one or more of: 1) >=50% decrease in number of lesions 2) complete flattening of >=50% of all raised lesions 3) >=50% decrease in the area of the 5 cutaneous marker lesions, compared to entry. Complete response determined by clinician as absence of any detectable residual KS disease, including tumor-associated edema.
  • Number of participants with early study discontinuation [ Time Frame: At weeks 48 and 96 ] [ Designated as safety issue: No ]
    Number of subjects who discontinued study prematurely due to any reason.
  • Time from initiation of delayed etoposide to initial KS partial response in Arm A [ Time Frame: From initiation of etoposide to 96 weeks ] [ Designated as safety issue: No ]
  • Time to initial Kaposi's sarcoma (KS) progression from study treatment initiation [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  • KS progression status at week 48 and at week 96 as dichotomous outcomes [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  • Occurrence of Grade >/= adverse events [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • IRIS events (both KS and non-KS related) [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Dose modifications [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  • Change in log10 HIV-1 plasma viral load from baseline at study visits [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  • Time to suppression of plasma HIV-1 RNA to < 400 copies/mL [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  • Change in peripheral blood C4+ lymphocyte cell count from baseline at study visits [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Antiretroviral Therapy (ART) Alone or With Delayed Chemo Versus ART With Immediate Chemo for Limited AIDS-related Kaposi's Sarcoma
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, your immune system, which fights infection and some cancers like KS, will get stronger. For some people, limited stage KS often improves or stays the same when they take ART. However, in some people KS gets worse when taking ART. These people may need chemotherapy at a later date.

This study is being 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 will also try 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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV-1 Infection
  • Kaposi's Sarcoma
  • Drug: efavirenz/emtricitabine/tenofovir disoproxil fumarate
    600 mg efavirenz/200 mg emtricitabine/300 mg tenofovir disoproxil fumarate taken orally at night
    Other Names:
    • Atripla®
    • EFV/FTC/TDF
  • Drug: etoposide
    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 will be escalated to 100 mg/day orally, days 1-7, every 2 weeks. A cycle can be delayed for a maximum of 14 days. ET must not be initiated prior to 7 days after the last dose in each cycle before starting the next cycle. ET may be administered up to a maximum of eight cycles (2 cycles during dose titration and 6 cycles at maximum dose). Participants who cannot tolerate escalation of the ET dose to 100 mg/day will be treated for a maximum of six cycles. Duration based on participant response to dosage.
    Other Names:
    • VePesid®
    • ET
  • Active Comparator: Arm A: Co-formulated EFV/FTC/TDF alone or with deferred ET
    Participants will receive co-formulated efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). At the discretion of the site investigator, after confirmation of disease progression by the IERC (Independent Endpoint Review Committee), participants who experience KS progression in Arm A will receive ET in addition to EFV/FTC/TDF. ET can be offered in Step 2 to participants randomized to Arm A in Step 1 whose KS progresses.
    Interventions:
    • Drug: efavirenz/emtricitabine/tenofovir disoproxil fumarate
    • Drug: etoposide
  • Active Comparator: Arm B: EFV/FTC/TDF and immediate ET
    Participants will receive co-formulated efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) with etoposide (ET) for 96 weeks.
    Interventions:
    • Drug: efavirenz/emtricitabine/tenofovir disoproxil fumarate
    • Drug: etoposide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
468
October 2019
October 2019   (final data collection date for primary outcome measure)

Step 1: Inclusion Criteria

  1. HIV-1 infection.
  2. Biopsy diagnostic of KS at any time prior to study entry.
  3. Current limited stage KS using the ACTG criteria documented in the study protocol. The following presentations of stage T1 KS are 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).
  4. A minimum of 5 cutaneous marker lesions
  5. Certain laboratory values obtained within 14 days prior to study entry.
  6. Female participants of reproductive potential must have a negative serum or urine pregnancy test performed within 7 days prior to study entry.
  7. All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization).
  8. Female participants who are participating in sexual activity that could lead to pregnancy must agree 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, and/or hormonal-based contraception.

    For Etoposide, confirmation of lack of reproductive potential is required for all participants. More information on this criterion can be found in the study protocol.

  9. Ability to swallow oral medications.
  10. Karnofsky performance score >= 60 within 30 days prior to entry.
  11. Ability and willingness of participant or legal guardian/representative to provide informed consent.
  12. Peripheral blood CD4+ lymphocyte cell count obtained within 30 days prior to study entry at a DAIDS-approved laboratory.
  13. 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.
  14. For participants who are to receive ART other than EFV/TDF/FTC, the availability of those ART components.

Step 2: Inclusion Criteria

  1. KS progression as defined in the study protocol or KS progression after a complete or partial response as defined in the study protocol, while on Step 1 Arm 1A, 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. Female participants of reproductive potential must have 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 agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization).
  9. Female participants who are participating in sexual activity that could lead to pregnancy must agree 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, hormonal-based contraception.

For Etoposide, confirmation of lack of reproductive potential is 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 1B or Arm 2A)

Step 1: Exclusion Criteria

  1. Any manifestation of KS which, in the opinion of the site investigator, requires immediate chemotherapy.
  2. Receipt of ART 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 PSWP.
  10. In the opinion of the site investigator, any psychological or social condition, or addictive disorder that would preclude compliance with the protocol.
  11. Current chronic, acute, or recurrent infections that are serious, in the opinion of the site investigator, for which the participant has not completed at least 14 days of therapy prior to study entry and/or is not clinically stable.

Step 2: Exclusion Criteria

  1. Current chronic, acute, or recurrent infections that are serious, in the opinion of the site investigator, for which the participant has not completed at least 14 days of therapy prior to initiating ET and/or is not clinically stable.
  2. Current or anticipated receipt of any of the prohibited medications indicated in the PSWP.
  3. Breastfeeding.

There are no exclusion criteria for Step 3.

Both
18 Years and older
No
Brazil,   Kenya,   Malawi,   Peru,   South Africa,   Uganda,   Zimbabwe
 
NCT01352117
ACTG A5264, 1U01AI068636
Yes
AIDS Clinical Trials Group
AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: Thomas B Campbell, M.D. University of Colorado Hospital CRS
Study Chair: Mina C Hosseinipour, M.D. University of North Carolina Lilongwe CRS
AIDS Clinical Trials Group
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP