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

Primary Purpose

HIV, AIDS, Kaposi's Sarcoma

Status
Completed
Phase
Phase 4
Locations
South Africa
Study Type
Interventional
Intervention
Generic HAART Triomune : d4T, 3TC, NVP
Generic HAART Triomune : d4T, 3TC, NVP and chemotherapy ABV
Sponsored by
University of KwaZulu
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV focused on measuring HIV, AIDS, Kaposi's sarcoma, Human herpesvirus 8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Department of Dermatology, King Edward VIII Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

HAART alone

Combination HAART and chemotherapy

Arm Description

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)

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.

Outcomes

Primary Outcome Measures

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.
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.
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.
Visceral: chest radiograph and endoscopy, where necessary, bronchoscopy
done in patients who presented with visceral KS at baseline to monitor the disease

Secondary Outcome Measures

Safety and toxicity by DAIDS Toxicity criteria
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
patients CD4 and VL will be measured 3 monthly to assess immunological and virological control
QOL by EORTC QLQ C30
EORTC QLQ C30 will be used as the tool to assess QOL in subjects
Adherence
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.

Full Information

First Posted
September 25, 2006
Last Updated
July 20, 2010
Sponsor
University of KwaZulu
Collaborators
AIDS Care Research in Africa, National Research Foundation, Singapore, AIDS Malignancy Consortium, Cipla Medpro, Dermatological Society of South Africa
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1. Study Identification

Unique Protocol Identification Number
NCT00380770
Brief Title
HIV/AIDS Kaposis Sarcoma: Comparison of Response to HAART vs HAART Plus CXT
Acronym
KAART
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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2009
Overall Recruitment Status
Completed
Study Start Date
January 2003 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
March 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University of KwaZulu
Collaborators
AIDS Care Research in Africa, National Research Foundation, Singapore, AIDS Malignancy Consortium, Cipla Medpro, Dermatological Society of South Africa

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
DETAILED METHODOLOGY PRIMARY OBJECTIVES: 1.To compare the clinical response of HIV KS at month 12 in patients treated with HAART alone with those treated with the combination of HAART and chemotherapy (CXT). SECONDARY OBJECTIVES To monitor safety, tolerance and adverse events associated with each regimen. To compare the impact of each regimen at baseline and months 12 on: CD4 count HIV1 viral load in blood HIV disease progression To compare the impact of each regimen on the patients Quality of life (QOL). To compare the impact of each regimen on the patients adherence to HAART. 5 To measure and compare HHV8 viral load and HHV8 specific CTL responses at baseline and month 12 to each regimen.(in blood and tissue specimens ) DESIGN Prospective, randomized, open- labeled trial RANDOMISATION Patients first staged into GOOD risk and POOR risk groups according to ACTG criteria. Thereafter 4 digit computer generated numbers after staging which assign patients to HAART alone or HAART plus CXT to ensure that equal numbers of GOOD and POOR risk patients are assigned to each group. 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. INTERVENTION 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) 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. This regimen will be given at 2 weekly intervals. This will be supplied by the Department of Oncology, KwaZulu Natal Province. PRIMARY ENDPOINTS Clinical response of KS Clinical photographs taken of marker lesions (5 according to AMC criteria) will be taken at baseline, month 6 and 12. Lesion measurement of 5 marker lesions (as per AMC RKS 02 )(www.amc.uab.edu) will be done at baseline, month 3, month 6, month 9 and month 12. 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. The patients will be assessed by a specialist dermatologist, trained to use the above instruments, and will be the same individual so as to decrease bias introduced with inter-observer variability. We recognize that there is the potential for bias as the study is not blinded and dermatologist will know patient assignment. For that reason, we are using established objective criteria to evaluate response. Biopsies will be performed at baseline, month 6 and month 12 to assist in confirming response and to evaluate HIV and HHV8 tissue viral loads Safety and toxicity by DAIDS Toxicity criteria QOL by EORTC QLQ C30 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV, AIDS, Kaposi's Sarcoma, Human Herpesvirus 8
Keywords
HIV, AIDS, Kaposi's sarcoma, Human herpesvirus 8

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
112 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HAART alone
Arm Type
Experimental
Arm Description
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)
Arm Title
Combination HAART and chemotherapy
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Generic HAART Triomune : d4T, 3TC, NVP
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Generic HAART Triomune : d4T, 3TC, NVP and chemotherapy ABV
Intervention Description
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.
Primary Outcome Measure Information:
Title
Clinical response of KS
Description
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.
Time Frame
3 monthly
Title
Skin: tumour measurements of 5 indicator skin lesions. Assessment of KS as per AMC RKS 02 (www.amc.uab.edu)
Description
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.
Time Frame
3 monthly
Title
photography of indicator lesions with metric tape in frame
Description
Clinical photographs taken of marker lesions (5 according to AMC criteria) will be taken at baseline, month 6 and 12.
Time Frame
6 monthly
Title
Visceral: chest radiograph and endoscopy, where necessary, bronchoscopy
Description
done in patients who presented with visceral KS at baseline to monitor the disease
Time Frame
6 monthly
Secondary Outcome Measure Information:
Title
Safety and toxicity by DAIDS Toxicity criteria
Description
DAAIDS toxicity criteria used to assess and measure severity of adverse events
Time Frame
as they occur
Title
Immunological and virological response to HAART as measured by CD4 and HIV-viral load
Description
patients CD4 and VL will be measured 3 monthly to assess immunological and virological control
Time Frame
3 monthly
Title
QOL by EORTC QLQ C30
Description
EORTC QLQ C30 will be used as the tool to assess QOL in subjects
Time Frame
3 monthly
Title
Adherence
Description
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.
Time Frame
monthly

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anisa Mosam, FC Derm,PhD
Organizational Affiliation
Nelson R Mandela School of Medicine, University of Kwazulu Natal
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Dermatology, King Edward VIII Hospital
City
Durban
State/Province
Kwazulu Natal
ZIP/Postal Code
4001
Country
South Africa

12. IPD Sharing Statement

Citations:
PubMed Identifier
16909181
Citation
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.
Results Reference
background
PubMed Identifier
15750399
Citation
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.
Results Reference
result
PubMed Identifier
15652610
Citation
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.
Results Reference
result
PubMed Identifier
15633090
Citation
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.
Results Reference
result
PubMed Identifier
17269969
Citation
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.
Results Reference
result
PubMed Identifier
30354935
Citation
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.
Results Reference
derived

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

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