Overview

This trial is active, not recruiting.

Conditions hiv-1 infection, kaposi's sarcoma
Treatments efavirenz/emtricitabine/tenofovir disoproxil fumarate, etoposide
Phase phase 3
Sponsor AIDS Clinical Trials Group
Collaborator National Institute of Allergy and Infectious Diseases (NIAID)
Start date October 2011
End date March 2016
Trial size 192 participants
Trial identifier NCT01352117, 1U01AI068636, ACTG A5264

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. 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
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.
efavirenz/emtricitabine/tenofovir disoproxil fumarate Atripla®
600 mg efavirenz/200 mg emtricitabine/300 mg tenofovir disoproxil fumarate taken orally at night
etoposide VePesid®
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.
(Active Comparator)
Participants will receive co-formulated efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) with etoposide (ET) for 96 weeks.
efavirenz/emtricitabine/tenofovir disoproxil fumarate Atripla®
600 mg efavirenz/200 mg emtricitabine/300 mg tenofovir disoproxil fumarate taken orally at night
etoposide VePesid®
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.

Primary Outcomes

Measure
Number of participants with Kaposi Sarcoma (KS) treatment response at week 48
time frame: 48 weeks

Secondary Outcomes

Measure
Time from study treatment initiation to initial KS partial response
time frame: From study treatment initiation to 96 weeks
Time from study treatment initiation to initial KS complete response
time frame: From study treatment initiation to 96 weeks
Time from study treatment initiation to initial KS partial or complete response
time frame: From study treatment initiation to 96 weeks
Number of participants with KS partial response
time frame: At weeks 48 and 96
Number of participants with KS complete response
time frame: At weeks 48 and 96
Number of participants with KS partial or complete response
time frame: At weeks 48 and 96
Number of participants with early study discontinuation
time frame: At weeks 48 and 96
Time from initiation of delayed etoposide to initial KS partial response in Arm A
time frame: From initiation of etoposide to 96 weeks
Time to initial Kaposi's sarcoma (KS) progression from study treatment initiation
time frame: 96 weeks
KS progression status at week 48 and at week 96 as dichotomous outcomes
time frame: 96 weeks
Occurrence of Grade >/= adverse events
time frame: 96 weeks
IRIS events (both KS and non-KS related)
time frame: 96 weeks
Dose modifications
time frame: 96 weeks
Change in log10 HIV-1 plasma viral load from baseline at study visits
time frame: 96 weeks
Time to suppression of plasma HIV-1 RNA to < 400 copies/mL
time frame: 96 weeks
Change in peripheral blood C4+ lymphocyte cell count from baseline at study visits
time frame: 96 weeks

Eligibility Criteria

Male or female participants at least 18 years old.

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.

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by AIDS Clinical Trials Group.