HIV/AIDS Kaposis Sarcoma: Comparison of Response to HAART vs HAART Plus CXT (KAART)
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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) |
- 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
- 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
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
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.
South Africa | |
Department of Dermatology, King Edward VIII Hospital | |
Durban, Kwazulu Natal, South Africa, 4001 |
Principal Investigator: | Anisa Mosam, FC Derm,PhD | Nelson R Mandela School of Medicine, University of Kwazulu Natal |
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