Three Chemo Regimens as an Adjunct to ART for Treatment of Advanced AIDS-KS

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by AIDS Clinical Trials Group
Sponsor:
Collaborators:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01435018
First received: September 14, 2011
Last updated: April 29, 2014
Last verified: April 2014

September 14, 2011
April 29, 2014
August 2013
June 2027   (final data collection date for primary outcome measure)
Lack of clinical efficacy [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Clinical efficacy is defined as Kaposi's Sarcoma (KS) progression, death by week 48, entry into an additional step prior to week 48, or loss to follow-up.
Same as current
Complete list of historical versions of study NCT01435018 on ClinicalTrials.gov Archive Site
  • Death by week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • KS progression by week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • AIDS-defining event by week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • HIV-1 RNA virologic failure by week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Virologic failure is defined as two successive measurements of plasma HIV-1 RNA ≥1000 copies/mL at week 12 to week 24 or RNA ≥400 copies/mL at week 24 or later.
  • Kaposi's Sarcoma-Immune Reconstitution Inflammatory Syndrome (KS-IRIS) by week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • KS tumor response by week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Duration of KS tumor response [ Time Frame: Throughout the study (7 years) ] [ Designated as safety issue: No ]
  • KS progression, death, or AIDS defining event by week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • KS progression, death, AIDS defining event, or virologic failure by week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • KS progression, death, AIDS defining event, virologic failure, or KS-IRIS by week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Time to KS progression or death [ Time Frame: Throughout the study (7 years) ] [ Designated as safety issue: No ]
  • Time to death [ Time Frame: Throughout the study (7 years) ] [ Designated as safety issue: No ]
  • Change in KS treatment by week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Chemotherapy-related toxicities and Adverse Events (AEs) (e.g., Peripheral Neuropathy (PN)) [ Time Frame: Throughout the study (7 years) ] [ Designated as safety issue: Yes ]
  • Changes in CD4+ lymphocyte cell count [ Time Frame: Baseline, weeks 60, 120, 180, 240, 300, 360 ] [ Designated as safety issue: No ]
  • Adherence to therapy [ Time Frame: Weeks 3, 6, 9, 12, 15, 18, 21, 24 ] [ Designated as safety issue: No ]
  • Plasma KS-associated herpesvirus (KSHV) [ Time Frame: Baseline, weeks 60, 120, 180, 240, 300, 360 ] [ Designated as safety issue: No ]
  • Salivary KSHV [ Time Frame: Baseline, weeks 60, 120, 180, 240, 300, 360 ] [ Designated as safety issue: No ]
  • Peripheral blood mononuclear cell (PBMC) KSHV [ Time Frame: Baseline, weeks 60, 120, 180, 240, 300, 360 ] [ Designated as safety issue: No ]
  • Presence of oral KS [ Time Frame: Throughout the study (7 years) ] [ Designated as safety issue: No ]
  • RNA levels for KSHV genes [ Time Frame: Baseline, weeks 60, 120, 180, 240, 300, 360 ] [ Designated as safety issue: No ]
  • Peripheral neuropathy (PN) [ Time Frame: Througout the study (7 years) ] [ Designated as safety issue: Yes ]
  • Symptomatic peripheral neuropathy (SPN) [ Time Frame: Throughout the study (7 years) ] [ Designated as safety issue: Yes ]
  • Immunohistochemical evaluations of viral and cellular gene expression [ Time Frame: baseline, 24-48 hours after 2nd chemo-therapy cycle begins ] [ Designated as safety issue: No ]
  • Quality of life measures [ Time Frame: Baseline, weeks 60, 120, 180, 240, 300, 360 ] [ Designated as safety issue: No ]
  • Cellular and humoral markers of immune function and activation [ Time Frame: Baseline, weeks 60, 120, 180, 240, 300, 360 ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Three Chemo Regimens as an Adjunct to ART for Treatment of Advanced AIDS-KS
A Randomized Comparison of Three Regimens of Chemotherapy With Compatible Antiretroviral Therapy for Treatment of Advanced AIDS-KS in Resource-Limited Settings

This study is being done to compare the safety and efficacy of three combination treatments for Kaposi's Sarcoma and AIDS.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV-1 Infection
  • Drug: Coformulated EFV/FTC/TDF

    The following ART regimens may be used:

    1. EFV/FTC/TDF (Atripla®) 200 mg/300 mg/600 mg orally once daily at bedtime or
    2. FTC/TDF 200 mg/300 mg (Truvada®) orally once daily at bedtime plus EFV (Stocrin®) 600 mg orally once daily at bedtime or
    3. FTC/TDF 200 mg/300 mg (Truvada®) orally once daily plus nevirapine (NVP) 200 mg orally twice daily or
    4. FTC/TDF 200 mg/300 mg (Truvada®) orally once daily plus PI/r at standard dosing
  • Drug: Etoposide

    Beginning on day one of the chemotherapy cycle, ET will be given orally in a dose of 50 mg twice daily for 7 consecutive days for the first cycle. If there is no Grade ≥ 2 toxicity attributable to ET after the first cycle, the dose will be escalated to 150 mg daily for 7 days in divided doses of 100 mg/50 mg for the second cycle. After the second cycle, if there is no Grade ≥ 2 toxicity attributable to ET, the dose will be escalated to 100 mg twice daily for 7 days for the third and subsequent cycles.

    Treatment with ET will continue for six cycles at the maximum dose achieved or until toxicity requiring discontinuation of study chemotherapy, or the site investigator, after consulting with the A5263/AMC 066 CMC, has determined that alternative therapy is required, whichever occurs first.

  • Drug: Bleomycin and Vincristine (BV)

    BV will be administered on day one of each chemotherapy cycle.

    Vincristine sulfate will be administered at a dose of 2 mg (fixed dose) in a volume of 2 mL over 1 minute into the sidearm of a rapidly flowing intravenous infusion every 3 weeks. The vincristine infusion will be followed by bleomycin as detailed below.

    Bleomycin sulfate will be administered at a dose of 15 units/m2 over 10 minutes every 3 weeks.

    Treatment with BV will continue for six cycles, or until toxicity requiring discontinuation of study chemotherapy, or the site investigator, after consulting with the A5263/AMC 066 CMC, has determined that alternative therapy is required, whichever occurs first.

  • Drug: Doxorubicin HCL Liposome Injection (PLD)

    Doxorubicin HCL liposome will be administered by IV infusion in 250 mL of 5% dextrose at a dose of 20 mg/ m2 body surface area every 3 weeks. The initial infusion rate should not exceed 1 mg/minute. The entire dose should be infused within 1 hour.

    Treatment with doxorubicin HCL liposome will continue for six cycles, or until toxicity requiring discontinuation of study chemotherapy, or the site investigator, after consulting with the A5263/AMC 066 CMC, has determined that alternative therapy is required, whichever occurs first.

  • Experimental: Arm 1A: Coformulated EFV/FTC/TDF plus ET
    Interventions:
    • Drug: Coformulated EFV/FTC/TDF
    • Drug: Etoposide
  • Experimental: Arm 1B: Coformulated EFV/FTC/TDF plus BV
    Interventions:
    • Drug: Coformulated EFV/FTC/TDF
    • Drug: Bleomycin and Vincristine (BV)
  • Experimental: Arm 1C: Coformulated EFV/FTC/TDF plus PLD
    Interventions:
    • Drug: Coformulated EFV/FTC/TDF
    • Drug: Doxorubicin HCL Liposome Injection (PLD)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
706
June 2027
June 2027   (final data collection date for primary outcome measure)

Inclusion Criteria for Step 1:

  • HIV-1 infection
  • Biopsy diagnostic of KS at any time prior to study entry.
  • Current KS stage T1 using ACTG criteria.
  • A minimum of five indicator KS cutaneous marker lesions plus an additional two lesions greater or equal to 4x4 mm that are accessible for punch biopsy.
  • CD4+ lymphocyte cell count obtained within 28 days prior to study entry at a DAIDS-approved laboratory.
  • Certain laboratory values, as defined in the protocol, obtained within 14 days prior to study entry.
  • Cardiac ejection fraction of greater than or equal to 50% obtained within 14 days prior to study entry.
  • Female study volunteers of reproductive potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL performed within 24 hours before initiating the protocol-specified medications.
  • All participants must agree not to participate in a conception process (active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization).
  • If participating in sexual activity that could lead to pregnancy, participant must agree that two reliable forms of contraceptives will be used simultaneously while receiving protocol-specified medications, and for 6 weeks after stopping the medications. Study volunteers who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy and/or bilateral oophorectomy or men who have documented azoospermia) are eligible without requiring the use of contraceptives.
  • Ability to swallow oral medications and adequate venous access.
  • Karnofsky performance status ≥ 60 within 28 days prior to entry.
  • Ability and willingness of participant or legal guardian/representative to provide informed consent.

Exclusion Criteria for Step 1:

  • Current chronic, acute, or recurrent serious infections for which the participant has not completed at least 14 days of therapy prior to Step 2 entry and/or is not clinically stable.
  • Serious illness requiring systemic treatment and/or hospitalization within 14 days prior to entry.
  • Current or history of known pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), emphysema, bronchiectasis, or diffuse or significant local radiographic interstitial infiltrates on chest x-ray (CXR) or computed axial tomography (CAT).
  • Oxygen saturation less than 90% and/or exercise desaturation greater than 4% within 14 days prior to study enrollment.
  • Grade ≥3 peripheral neuropathy (PN) at entry.
  • Breastfeeding.
  • Receipt of ART for more than 28 days immediately prior to entry.
  • Prior or current systemic or locally administered chemotherapy.
  • Prior or current radiation therapy.
  • Prior or current immunotherapy, e.g., interferon alfa.
  • Corticosteroid use at doses above those given as replacement therapy for adrenal insufficiency within the last 30 days prior to study entry.
  • Any immunomodulator, HIV vaccine, live attenuated vaccines, or other investigational therapy or investigational vaccine within 30 days prior to study entry.
  • Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
  • Active drug or alcohol use or dependence that would interfere with adherence to study requirements.
  • Current or anticipated receipt of any of the prohibited medications listed in section 5.5.2 of the protocol.
  • In the opinion of the investigator, any psychological or social condition, or addictive disorder that would preclude compliance with the protocol.
  • New York Heart Association Functional Class II-IV heart failure.
Both
18 Years and older
No
South Africa,   Brazil,   Kenya,   Uganda,   Malawi,   Zimbabwe
 
NCT01435018
ACTG A5263, 1U01AI068636, U01CA121947
Yes
AIDS Clinical Trials Group
AIDS Clinical Trials Group
  • National Institute of Allergy and Infectious Diseases (NIAID)
  • National Cancer Institute (NCI)
  • National Institute of Dental and Craniofacial Research (NIDCR)
Study Chair: Margaret Borok-Williams, MD University of Zimbabwe
Study Chair: Susan E Krown, MD AIDS Malignancy Consortium
AIDS Clinical Trials Group
April 2014

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