Kaposi's SarcomaPhase 4ARKSNCT00444379
Anti-Retrovirals for Kaposi's Sarcoma
A Phase 4 study testing Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovir in people with Kaposi's Sarcoma and HIV Infections, run by University of California, San Francisco at 1 site in Uganda.
Trial summary
The primary purpose of this study is to determine whether a protease inhibitor-based antiretroviral regimen is more efficacious than a non-nucleoside reverse transcriptase inhibitor-based antiretroviral regimen in promoting the regression of KS tumor burden in persons with AIDS-related KS in Africa. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kaposi's Sarcoma, HIV Infections
- What is being tested?
- Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 224 participants
- Where
- 1 siteUganda
- Study dates
- Apr 2007to Jul 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older
- HIV-1 infection
- No prior antiretroviral therapy of any duration, including prior use to prevent perinatal transmission within prior six months.
- No prior chemotherapy or radiotherapy for KS
- Presence of Kaposi's sarcoma, documented by biopsy by the Pathology Department at Mulago Hospital, with at least one mucocutaneous lesion (including oral or genital mucosal lesions), each at least 0.6 x 0.6 cm in perpendicular diameters.
- Laboratory values obtained within 21 days prior to randomization: absolute neutrophil count equal to or more than 1000/mm3; hemoglobin > 9.0 g/dL; platelet count > 50,000/mm3; creatinine < 2 times upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 times ULN; and alkaline phosphatase and total bilirubin < 2 times ULN.
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- In women, negative urine pregnancy test within 28 days of randomization and just before randomization.
- If a woman of child-bearing potential (i.e., not yet reached menopause or undergone hysterectomy, bilateral oophorectomy, or tubal ligation), must be willing to use at least two of the following methods of contraception, to be provided by the study: condoms (male or female), IUD, or hormone-based therapy, e.g., contraceptive pills, Norplant or Depo-Provera.
- Candidate currently resides within Uganda and does not intend to relocate away from current geographical area of residence for the duration of study participation.
- Karnofsky performance score of 70 or more
Who cannot join
- Extensive degree of mucocutaneous KS, which would typically require chemotherapy or radiotherapy. This is defined by any of the following:
- One or more bulky cutaneous lesions, defined as at least 5.0 cm in greatest diameter across the surface of the skin and at least 3 cm in height
- One or more mucocutaneous lesions exhibiting ulceration
- One or more oral lesions that interfere with swallowing
- Suggestion of pulmonary or gastrointestinal visceral KS, as evidenced by any of the following:
- Abnormal chest x-ray within 21 days prior to randomization which is otherwise unexplained, unless the x-ray is unchanged compared with at least 60 days earlier
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- Positive occult blood stool testing within 21 days prior to randomization or history of overt bleeding from the mouth or rectum in the 21 days prior to randomization
- Facial lymphedema or lymphedema in any other body region which causes symptoms (e.g., pain) or functional disability (e.g., any less than 85% active range of motion in a large joint)
- Evidence of currently active, untreated opportunistic infection or malignancy (not including Kaposi's sarcoma); or unexplained temperature which is > 38.5 degrees C
- Use of drugs, within the prior 28 days, contraindicated while taking lopinavir/ritonavir or efavirenz because of effects on the cytochrome P450 system. These include propafenone, astemizole, terfenadine, rifampin, rifapentine, ergot derivatives, cisapride, lovastatin, simvastatin, pimozide, midazolam, and triazolam.
- Active drug or alcohol use that, in the investigators' opinion, would interfere with study participation
- Breastfeeding
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Comparison of Protease Inhibitor-based Versus Non-nucleoside Reverse Transcriptase Inhibitor-based Antiretroviral Therapy for Initial Treatment of Individuals With AIDS-related Kaposi's Sarcoma in Sub-Saharan Africa
The primary purpose of this study is to determine whether a protease inhibitor-based antiretroviral regimen is more efficacious than a non-nucleoside reverse transcriptase inhibitor-based antiretroviral regimen in promoting the regression of KS tumor burden in persons with AIDS-related KS in Africa.
Read the detailed description
With the advent of the HIV epidemic, Kaposi's sarcoma (KS) is now the most common adult cancer in many parts of sub-Saharan Africa. In HIV-infected patients with KS in developed settings, the initiation of highly active anti-retroviral therapy (HAART) has been associated with regression of the tumor, in many but not all cases, even in the absence of conventional chemotherapy. However, it is not known which specific antiretroviral drugs or regimens are critical to convey HAART's anti-KS effect. In particular, it is not known whether the anti-KS effects of protease inhibitors (PI) in vitro and in animal models translate into improved clinical outcomes as compared to non-PI-based HAART regimens. To address this, we will determine whether a PI-based HAART regimen (lopinavir/ritonavir plus emtricitabine/tenofovir) is superior to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART regimen (efavirenz plus emtricitabine/tenofovir) in promoting the regression of KS tumor burden in persons with AIDS-related KS in sub-Saharan Africa. We will enroll 224 patients with AIDS-related KS in Kampala, Uganda, randomly assign them to either a PI-based HAART or an NNRTI-based HAART regimen, and observe them for one year to determine the response in their KS to therapy.
- Conditions
- Kaposi's Sarcoma, HIV Infections
- Being tested
- Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovir
- Keywords
- Kaposi's sarcoma, KSHV, AIDS, HHV-8, treatment naive
- Medical subject headings
- Sarcoma, Kaposi, HIV Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/TenofovirDrug
Also called Lopinavir/ritonavir Aluvia (ALUABT), Efavirenz Stocrin (EFVBMM), Emtricitabine/Tenofovir Truvada (TRUGLD)
Lopinavir/ritonavir 200/50mg plus Emtricitabine/Tenofovir 200/300mg versus Efavirenz 600mg plus Emtricitabine/Tenofovir 200/300mg
| Study group | Role | What they receive |
|---|---|---|
| PI-based HAART regimen | Active comparator | PI-based HAART regimen (lopinavir/ritonavir plus emtricitabine/tenofovir) Receives: Drug: Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovir |
| non-nucleoside reverse transcriptase inhibitor | Active comparator | non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART regimen (efavirenz plus emtricitabine/tenofovir) Receives: Drug: Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blinded assessment of the change in the burden of KS lesions
survival
Secondary outcomes (5)
CD4+ T cell count and HIV plasma HIV RNA levels
KSHV DNA levels in saliva and blood
Humoral and cellular KSHV immune response markers
Quality-of-life assessment
Incidence of Kaposi's sarcoma-associated Immune Reconstitution Inflammatory Syndrome (KS-IRIS)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2007 (estimated)
- Study startApr 2007
- Primary completionFeb 2012
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kaposi's SarcomaStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 224 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), Gilead Sciences, Abbott, Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Dr. Jeffrey N Martin, MD, MPH, Principal investigator, University of California, San FranciscoDr. Edward K Mbidde, MBChB, MMed, Principal investigator, MRC/UVRI and LSHTM Uganda Research Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00444379
- Sponsor's protocol ID
- NIH/NCI Grant #: R01 CA119903
- Acronym
- ARKS
- Status last verified
- Aug 2014
- First submitted
- 6 Mar 2007
- Last updated
- 20 Aug 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Comparison of Protease Inhibitor-based Versus Non-nucleoside Reverse Transcriptase Inhibitor-based Antiretroviral Therapy for Initial Treatment of Individuals With AIDS-related Kaposi's Sarcoma in Sub-Saharan Africa
- ClinicalTrials.gov ID
- NCT00444379
- Acronym / sponsor ID
- ARKS / NIH/NCI Grant #: R01 CA119903
- Conditions
- Kaposi's Sarcoma, HIV Infections
- Keywords
- Kaposi's sarcoma, KSHV, AIDS, HHV-8, treatment naive
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 224 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), Gilead Sciences, Abbott, Merck Sharp & Dohme LLC
- Study start
- Apr 2007
- Primary completion
- Feb 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 7 Mar 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to determine whether a protease inhibitor-based antiretroviral regimen is more efficacious than a non-nucleoside reverse transcriptase inhibitor-based antiretroviral regimen in promoting the regression of KS tumor burden in persons with AIDS-related KS in Africa.
Detailed description
With the advent of the HIV epidemic, Kaposi's sarcoma (KS) is now the most common adult cancer in many parts of sub-Saharan Africa. In HIV-infected patients with KS in developed settings, the initiation of highly active anti-retroviral therapy (HAART) has been associated with regression of the tumor, in many but not all cases, even in the absence of conventional chemotherapy. However, it is not known which specific antiretroviral drugs or regimens are critical to convey HAART's anti-KS effect. In particular, it is not known whether the anti-KS effects of protease inhibitors (PI) in vitro and in animal models translate into improved clinical outcomes as compared to non-PI-based HAART regimens. To address this, we will determine whether a PI-based HAART regimen (lopinavir/ritonavir plus emtricitabine/tenofovir) is superior to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART regimen (efavirenz plus emtricitabine/tenofovir) in promoting the regression of KS tumor burden in persons with AIDS-related KS in sub-Saharan Africa. We will enroll 224 patients with AIDS-related KS in Kampala, Uganda, randomly assign them to either a PI-based HAART or an NNRTI-based HAART regimen, and observe them for one year to determine the response in their KS to therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PI-based HAART regimen | Active comparator | Drug: Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/TenofovirPI-based HAART regimen (lopinavir/ritonavir plus emtricitabine/tenofovir) |
| non-nucleoside reverse transcriptase inhibitor | Active comparator | Drug: Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovirnon-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART regimen (efavirenz plus emtricitabine/tenofovir) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age 18 years or older
- HIV-1 infection
- No prior antiretroviral therapy of any duration, including prior use to prevent perinatal transmission within prior six months.
- No prior chemotherapy or radiotherapy for KS
- Presence of Kaposi's sarcoma, documented by biopsy by the Pathology Department at Mulago Hospital, with at least one mucocutaneous lesion (including oral or genital mucosal lesions), each at least 0.6 x 0.6 cm in perpendicular diameters.
Key exclusion criteria (12 listed)
- Extensive degree of mucocutaneous KS, which would typically require chemotherapy or radiotherapy. This is defined by any of the following:
- Suggestion of pulmonary or gastrointestinal visceral KS, as evidenced by any of the following:
- Facial lymphedema or lymphedema in any other body region which causes symptoms (e.g., pain) or functional disability (e.g., any less than 85% active range of motion in a large joint)
- Evidence of currently active, untreated opportunistic infection or malignancy (not including Kaposi's sarcoma); or unexplained temperature which is > 38.5 degrees C
- Use of drugs, within the prior 28 days, contraindicated while taking lopinavir/ritonavir or efavirenz because of effects on the cytochrome P450 system. These include propafenone, astemizole, terfenadine, rifampin, rifapentine, ergot derivatives, cisapride, lovastatin, simvastatin, pimozide, midazolam, and triazolam.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/TenofovirAlso: Lopinavir/ritonavir Aluvia (ALUABT), Efavirenz Stocrin (EFVBMM), Emtricitabine/Tenofovir Truvada (TRUGLD)Lopinavir/ritonavir 200/50mg plus Emtricitabine/Tenofovir 200/300mg versus Efavirenz 600mg plus Emtricitabine/Tenofovir 200/300mg | Drug | PI-based HAART regimen, non-nucleoside reverse transcriptase inhibitor |
Primary outcome
Blinded assessment of the change in the burden of KS lesions
survival
5 secondary outcomes
CD4+ T cell count and HIV plasma HIV RNA levels
KSHV DNA levels in saliva and blood
Humoral and cellular KSHV immune response markers
Quality-of-life assessment
Incidence of Kaposi's sarcoma-associated Immune Reconstitution Inflammatory Syndrome (KS-IRIS)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2014.
- Medline Plus- Health InformationLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr. Jeffrey N Martin, MD, MPH principal investigator
University of California, San Francisco
Dr. Edward K Mbidde, MBChB, MMed principal investigator
MRC/UVRI and LSHTM Uganda Research Unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovir in people with Kaposi's Sarcoma and HIV Infections, run by University of California, San Francisco at 1 site in Uganda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blinded assessment of the change in the burden of KS lesions. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2014.