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

• Status: Completed
• Trial end date: 2009-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of KwaZulu
• Collaborators: AIDS Care Research in Africa; AIDS Malignancy Consortium; Cipla Medpro; Dermatological Society of South Africa; National Research Foundation, Singapore
• Treatments: Lamivudine; Nevirapine; Stavudine; Stavudine, lamivudine, nevirapine drug combination

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.