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

NCT00380770 | Completed Phase 4 DMC

• 1 other identifier: H029/02
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV; AIDS; Kaposi's Sarcoma; Human Herpesvirus 8

Keywords

HIV; AIDS; Kaposi's sarcoma; Human herpesvirus 8

Outcome Measures

Primary Outcomes (4)

• Clinical response of KS

  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.

  3 monthly

• Skin: tumour measurements of 5 indicator skin lesions. Assessment of KS as per AMC RKS 02 (www.amc.uab.edu)

  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.

  3 monthly

• photography of indicator lesions with metric tape in frame

  Clinical photographs taken of marker lesions (5 according to AMC criteria) will be taken at baseline, month 6 and 12.

  6 monthly

• Visceral: chest radiograph and endoscopy, where necessary, bronchoscopy

  done in patients who presented with visceral KS at baseline to monitor the disease

  6 monthly

Secondary Outcomes (4)

• Safety and toxicity by DAIDS Toxicity criteria

  as they occur

• Immunological and virological response to HAART as measured by CD4 and HIV-viral load

  3 monthly

• QOL by EORTC QLQ C30

  3 monthly

• Adherence

  monthly

Study Arms (2)

HAART alone

EXPERIMENTAL

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

Combination HAART and chemotherapy

ACTIVE COMPARATOR

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

Interventions

Generic HAART Triomune : d4T, 3TC, NVP DRUG

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)

HAART alone

Generic HAART Triomune : d4T, 3TC, NVP and chemotherapy ABV DRUG

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.

Combination HAART and chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of KwaZulu: lead
• AIDS Care Research in Africa: collaborator
• National Research Foundation, Singapore: collaborator
• AIDS Malignancy Consortium: collaborator
• Cipla Medpro: collaborator
• Dermatological Society of South Africa: collaborator

Study Sites (1)

Department of Dermatology, King Edward VIII Hospital

Durban, KwaZulu-Natal, 4001, South Africa

Location

Related Publications (6)

• Sebitloane HM, Mosam A, Moodley J. Disseminated AIDS-associated Kaposi's sarcoma in pregnancy. S Afr Med J. 2006 Jul;96(7):602-3. No abstract available.

  PMID: 16909181 BACKGROUND

• Mosam A, Cassol E, Page T, Bodasing U, Cassol S, Dawood H, Friedland GH, Scadden DT, Aboobaker J, Jordaan JP, Lalloo UG, Esterhuizen TM, Coovadia HM. Generic antiretroviral efficacy in AIDS-associated Kaposi's sarcoma in sub-Saharan Africa. AIDS. 2005 Mar 4;19(4):441-3. doi: 10.1097/01.aids.0000161775.36652.85.

  PMID: 15750399 RESULT

• Mosam A, Goga Y, Thejpal R, Cassol E, Page T, Cassol S, Aboobaker J, Coovadia HM. Lymphadenopathy, pneumonia, and HIV--a common trio, an uncommon outcome. Lancet. 2005 Jan 15-21;365(9455):266. doi: 10.1016/S0140-6736(05)17747-2. No abstract available.

  PMID: 15652610 RESULT

• Cassol E, Page T, Mosam A, Friedland G, Jack C, Lalloo U, Kopetka J, Patterson B, Esterhuizen T, Coovadia HM. Therapeutic response of HIV-1 subtype C in African patients coinfected with either Mycobacterium tuberculosis or human herpesvirus-8. J Infect Dis. 2005 Feb 1;191(3):324-32. doi: 10.1086/427337. Epub 2004 Dec 22.

  PMID: 15633090 RESULT

• Peer FI, Pui MH, Mosam A, Rae WI. 99mTc-MIBI imaging of cutaneous AIDS-associated Kaposi's sarcoma. Int J Dermatol. 2007 Feb;46(2):166-71. doi: 10.1111/j.1365-4632.2006.03001.x.

  PMID: 17269969 RESULT

• Shaik F, Uldrick TS, Esterhuizen T, Mosam A. Health-Related Quality of Life in Patients Treated With Antiretroviral Therapy Only Versus Chemotherapy and Antiretroviral Therapy for HIV-Associated Kaposi Sarcoma: A Randomized Control Trial. J Glob Oncol. 2018 Oct;4:1-9. doi: 10.1200/JGO.18.00105.

  PMID: 30354935 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Sarcoma, Kaposi

Interventions

Nevirapine

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Herpesviridae Infections; DNA Virus Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Anisa Mosam, FC Derm,PhD

  Nelson R Mandela School of Medicine, University of Kwazulu Natal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 25, 2006
• First Posted: September 26, 2006
• Study Start: January 1, 2003
• Primary Completion: February 1, 2009
• Study Completion: March 1, 2009
• Last Updated: July 21, 2010

Record last verified: 2009-03

Locations

ZA (1)