HIV/AIDS Kaposis Sarcoma: Comparison of Response to HAART vs HAART Plus CXT (KAART)

This study has been completed.
Sponsor:
Collaborators:
AIDS Care Research in Africa
National Research Foundation, Singapore
AIDS Malignancy Consortium
Cipla Medpro
Dermatological Society of South Africa
Information provided by:
University of KwaZulu
ClinicalTrials.gov Identifier:
NCT00380770
First received: September 25, 2006
Last updated: July 20, 2010
Last verified: March 2009
  Purpose

Kaposi's sarcoma (KS)is the commonest malignancy associated with HIV/AIDS. Therapy for this cancer, which causes substantial morbidity, is suboptimal in resource poor settings. The reasons for this are: advanced state of immunosuppression when patients present for clinical care, concomitant opportunistic infections, non- availability of antiretroviral therapy (ART), non-availability and toxicity of chemotherapy (CXT), when available, in patients with full blown AIDS, prohibitive costs of bone marrow support and fiscal constraints in resource poor settings.

A recent Cochrane Review assessed the effectiveness of current therapeutic regimens for HIV KS, with a focus on options available in resource poor settings. The major selection criteria for this review were randomized controlled trials for HIV KS in adults. The main conclusions were that data from randomized controlled trials on effective treatments for HIV KS are sparse, particularly among people who are also taking highly active antiretroviral therapy (HAART). Alitretinoin gel is effective for therapy of cutaneous lesions, pegylated liposomal doxorubicin is effective for advanced KS and radiotherapy is effective for treating cutaneous lesions. Apart from the randomized trial of radiotherapy, no trials applicable to developing settings were identified. Therapy of HIV KS in developing countries thus remains unanswered.

The authors concluded that therapies discussed in the review are unlikely to be available or affordable in developing countries where the bulk of HIV infection and KS occur, apart from radiotherapy at a few tertiary centers. However, recent changes in pricing due to the global alliance and access initiatives mean that HAART is likely to be more available and accessible to developing countries in the near future. South Africa now has committed to this at cabinet level and had a task force to address this issue.

HAART has been proposed as therapy for HIV KS on the basis of restoring immune competence and minimizing the HIV tat drive to KS formation. It also improves immunologic control of HHV 8 possibly through interrupting the HIV-1- HHV-8 interaction.

There has been only one randomised trial conducted in Spain which compared HAART to the combination of HAART and CXT. There is to date no prospective, randomised controlled trial which compares the efficacy of HAART to the standard of care in HIV KS in Africa.


Condition Intervention Phase
HIV
AIDS
Kaposi's Sarcoma
Human Herpesvirus 8
Drug: Generic HAART Triomune : d4T, 3TC, NVP
Drug: Generic HAART Triomune : d4T, 3TC, NVP and chemotherapy ABV
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective Randomized Trial Comparing the Response of HIV Kaposi's Sarcoma (KS) to HAART Versus the Combination of HAART and Chemotherapy (CXT)

Resource links provided by NLM:


Further study details as provided by University of KwaZulu:

Primary Outcome Measures:
  • Clinical response of KS [ Time Frame: 3 monthly ] [ Designated as safety issue: No ]
    Responses will be categorized as complete response(only with biopsy confirmation), complete clinical response, partial response, stable disease and disease progression according to ACTG criteria.

  • Skin: tumour measurements of 5 indicator skin lesions. Assessment of KS as per AMC RKS 02 (www.amc.uab.edu) [ Time Frame: 3 monthly ] [ Designated as safety issue: No ]
    Measurement of the same 5 marker lesions (as per AMC RKS 02 )will be done at baseline, month 3, month 6, month 9 and month 12. Assessed by bi-directional diameter.

  • photography of indicator lesions with metric tape in frame [ Time Frame: 6 monthly ] [ Designated as safety issue: No ]
    Clinical photographs taken of marker lesions (5 according to AMC criteria) will be taken at baseline, month 6 and 12.

  • Visceral: chest radiograph and endoscopy, where necessary, bronchoscopy [ Time Frame: 6 monthly ] [ Designated as safety issue: No ]
    done in patients who presented with visceral KS at baseline to monitor the disease


Secondary Outcome Measures:
  • Safety and toxicity by DAIDS Toxicity criteria [ Time Frame: as they occur ] [ Designated as safety issue: Yes ]
    DAAIDS toxicity criteria used to assess and measure severity of adverse events

  • Immunological and virological response to HAART as measured by CD4 and HIV-viral load [ Time Frame: 3 monthly ] [ Designated as safety issue: No ]
    patients CD4 and VL will be measured 3 monthly to assess immunological and virological control

  • QOL by EORTC QLQ C30 [ Time Frame: 3 monthly ] [ Designated as safety issue: No ]
    EORTC QLQ C30 will be used as the tool to assess QOL in subjects

  • Adherence [ Time Frame: monthly ] [ Designated as safety issue: No ]
    Adherence by 7 day adherence questionnaire Adherence will be measured using a standardized validated self administered questionnaire, which enables review of each medication during previous 7 days and a medication specific and overall adherence score.


Enrollment: 112
Study Start Date: January 2003
Study Completion Date: March 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HAART alone
Arm 1. HAART These patients will be given one tablet twice daily of Triomune® (Cipla, Mumbai) Stavudine 40mg b.d > 60 kg , 30mg bd <60kg Lamivudine 150mg b.d > 50 kg 2mg/kg < 50 kg Nevirapine 200mg b.d ( 200mg daily for first 2 weeks)
Drug: Generic HAART Triomune : d4T, 3TC, NVP
Triomune® (Cipla, Mumbai) Stavudine 40mg b.d > 60 kg , 30mg bd <60kg Lamivudine 150mg b.d > 50 kg 2mg/kg < 50 kg Nevirapine 200mg b.d ( 200mg daily for first 2 weeks)
Active Comparator: Combination HAART and chemotherapy
Arm 2. CTX PLUS HAART. HAART will be given as above. In addition, CTX will be administered at 2 weekly intervals in the Oncology Dept at KEH VIII Hospital and will consist of:- Intramuscular Bleomycin 10 U/m2 ; Intravenous Vincristine 1.4mg/m2 maximum 2mg and Intravenous Doxorubicin 20mg/m2.
Drug: Generic HAART Triomune : d4T, 3TC, NVP and chemotherapy ABV
Triomune® (Cipla, Mumbai) Stavudine 40mg b.d > 60 kg , 30mg bd <60kg Lamivudine 150mg b.d > 50 kg 2mg/kg < 50 kg Nevirapine 200mg b.d ( 200mg daily for first 2 weeks) Intramuscular Bleomycin 10 U/m2 ; Intravenous Vincristine 1.4mg/m2 maximum 2mg and Intravenous Doxorubicin 20mg/m2.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent
  • Adults > 18 years
  • Documented HIV positive status (Confirmed by two ELISAs and HIV-1 RNA testing)
  • Willingness to use a barrier method of birth control throughout the course of the study, because of potential drug interactions that make oral contraceptives less effective (for women of childbearing potential) and sexually active males
  • Histologically proven
  • At least five measurable, previously unirradiated cutaneous lesions must be present which can be used as indicator lesions.
  • ECOG performance status 0-2

Exclusion Criteria:

  • • Pregnancy or breastfeeding

    • Fungating tumors of KS
    • Symptomatic pulmonary KS
    • Symptomatic GI tract KS
    • Clinical evidence of peripheral neuropathy
    • Clinical evidence of heart disease
    • Total neutrophil count of < 1,000u/L, Hemoglobin < 9.0gm/dl or platelet count of < 75,000u/L; serum creatinine > 1.5mgh/dl, direct serum bilirubin > 85 umol/l, AST or ALT > 2.5 time ULN.
    • Prior HAART ( to fairly evaluate antiretroviral response and KS response to HAART, patients should be antiretroviral naïve)
    • Prior radiation therapy for KS to sites of indicator lesions.
    • Prior cytotoxic chemotherapy for KS.
    • Concurrent neoplasia requiring cytotoxic therapy.
    • Life expectancy of < 3 months.
    • Circumstances, which in the opinion of the investigator make it unlikely the patient, can comply with the safety monitoring required for participation in this trial.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00380770

Locations
South Africa
Department of Dermatology, King Edward VIII Hospital
Durban, Kwazulu Natal, South Africa, 4001
Sponsors and Collaborators
University of KwaZulu
AIDS Care Research in Africa
National Research Foundation, Singapore
AIDS Malignancy Consortium
Cipla Medpro
Dermatological Society of South Africa
Investigators
Principal Investigator: Anisa Mosam, FC Derm,PhD Nelson R Mandela School of Medicine, University of Kwazulu Natal
  More Information

Publications:
Responsible Party: Dr Anisa Mosam, Department of Dermatology UKZN
ClinicalTrials.gov Identifier: NCT00380770     History of Changes
Other Study ID Numbers: H029/02
Study First Received: September 25, 2006
Last Updated: July 20, 2010
Health Authority: South Africa: Medicines Control Council

Keywords provided by University of KwaZulu:
HIV
AIDS
Kaposi's sarcoma
Human herpesvirus 8

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Sarcoma, Kaposi
Sarcoma
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Herpesviridae Infections
DNA Virus Infections
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Vascular Tissue

ClinicalTrials.gov processed this record on February 21, 2013