Three Chemo Regimens as an Adjunct to ART for Treatment of Advanced AIDS-KS
Information source: AIDS Clinical Trials Group
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV-1 Infection
Intervention: Coformulated EFV/FTC/TDF (Drug); Etoposide (Drug); Bleomycin and Vincristine (BV) (Drug); Paclitaxel (PTX) (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: AIDS Clinical Trials Group Official(s) and/or principal investigator(s):
Margaret Borok-Williams, MD, Study Chair, Affiliation: University of Zimbabwe
Susan E Krown, MD, Study Chair, Affiliation: AIDS Malignancy Consortium
Summary
This study is being done to compare the safety and efficacy of three combination treatments
for Kaposi's Sarcoma and AIDS.
Clinical Details
Official title: A Randomized Comparison of Three Regimens of Chemotherapy With Compatible Antiretroviral Therapy for Treatment of Advanced AIDS-KS in Resource-Limited Settings
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Lack of clinical efficacy
Secondary outcome: Death by week 48KS progression by week 48 AIDS-defining event by week 48 HIV-1 RNA virologic failure by week 48 Kaposi's Sarcoma-Immune Reconstitution Inflammatory Syndrome (KS-IRIS) by week 48 KS tumor response by week 48 Duration of KS tumor response KS progression, death, or AIDS defining event by week 48 KS progression, death, AIDS defining event, or virologic failure by week 48 KS progression, death, AIDS defining event, virologic failure, or KS-IRIS by week 48 Time to KS progression or death Time to death Change in KS treatment by week 48 Chemotherapy-related toxicities and Adverse Events (AEs) (e.g., Peripheral Neuropathy (PN)) Changes in CD4+ lymphocyte cell count Adherence to therapy Plasma KS-associated herpesvirus (KSHV) Salivary KSHV Peripheral blood mononuclear cell (PBMC) KSHV Presence of oral KS RNA levels for KSHV genes Peripheral neuropathy (PN) Symptomatic peripheral neuropathy (SPN) Immunohistochemical evaluations of viral and cellular gene expression Quality of life measures Cellular and humoral markers of immune function and activation
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
Instituto de Pesquisa Clinica Evandro Chagas (12101), Rio de Janeiro 21045, Brazil; Recruiting
Sandra W. Cardoso, Phone: 552-125-644933, Email: sandra.wagner@bol.com.br
Beatriz Grinsztejn, MD, PhD, Principal Investigator
Moi University International Clnical Trials Unit, Eldoret 30100, Kenya; Recruiting
Kipruto Kirwa, Phone: 254-53-20-60850, Email: kkr380@yahoo.com
KMRI / Walter Reed Project Clinical Research Center, Kericho, Kenya; Recruiting
Hellen Ngeno, Phone: (254 52) 30686, Email: hngeno@wrp-kch.org
Univ. of Malawi, John Hopkins Project, Blantyre, Malawi; Recruiting
Sima TM Berendes, MPH, Phone: 265-018-60132, Email: sberendes@jhu.medcol.mw
Johnstone Kumwenda, MD, Principal Investigator
Durban Adult HIV CRS (11201), Durban 4013 SF, South Africa; Recruiting
Fawzia Williamson, Phone: 27 31 260 4365, Email: amodf1@nu.ac.za
Umesh Gangaram Lalloo, MD, FRCP, Principal Investigator
University of Witwatersrand, Johannesburg, South Africa; Recruiting
Pauline S Vunandlala, BSc., Phone: 27 11 717 2810, Email: idsyndicate@witshealth.co.za
Uganda Cancer Institute ACTG CRS, Kampala, Uganda; Recruiting
Jackson Orem, MB, ChB, MMED, Phone: 256-414540410
UZ-Parirenyatwa CRS (30313), Harare, Zimbabwe; Recruiting
Jimijika Batani, B.A., Phone: 263-912272818, Email: jbatani@uz-ucsf.co.zw
James Hakim, MD, MSc, FRCP, Principal Investigator
Additional Information
Starting date: August 2013
Last updated: July 6, 2015
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