Anti-Retrovirals for Kaposi's Sarcoma (ARKS)

This study has been completed.
Sponsor:
Collaborators:
Gilead Sciences
Abbott
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00444379
First received: March 6, 2007
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Kaposi's Sarcoma
HIV Infections
Drug: Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Blinded assessment of the change in the burden of KS lesions
    survival


Secondary Outcome Measures:
  • 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)

Enrollment: 224
Study Start Date: April 2007
Study Completion Date: July 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: PI-based HAART regimen
PI-based HAART regimen (lopinavir/ritonavir plus emtricitabine/tenofovir)
Drug: Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovir
Lopinavir/ritonavir 200/50mg plus Emtricitabine/Tenofovir 200/300mg versus Efavirenz 600mg plus Emtricitabine/Tenofovir 200/300mg
Other Names:
  • Lopinavir/ritonavir Aluvia (ALUABT)
  • Efavirenz Stocrin (EFVBMM)
  • Emtricitabine/Tenofovir Truvada (TRUGLD)
Active Comparator: non-nucleoside reverse transcriptase inhibitor
non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART regimen (efavirenz plus emtricitabine/tenofovir)
Drug: Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovir
Lopinavir/ritonavir 200/50mg plus Emtricitabine/Tenofovir 200/300mg versus Efavirenz 600mg plus Emtricitabine/Tenofovir 200/300mg
Other Names:
  • Lopinavir/ritonavir Aluvia (ALUABT)
  • Efavirenz Stocrin (EFVBMM)
  • Emtricitabine/Tenofovir Truvada (TRUGLD)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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

Exclusion Criteria:

  • 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
    • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00444379

Locations
Uganda
Infectious Diseases Institute, Mulago Hospital
Kampala, Uganda
Sponsors and Collaborators
University of California, San Francisco
Gilead Sciences
Abbott
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Dr. Jeffrey N Martin, MD, MPH University of California, San Francisco
Principal Investigator: Dr. Edward K Mbidde, MBChB, MMed MRC/UVRI Uganda Research Unit on Aids
  More Information

Additional Information:
No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00444379     History of Changes
Other Study ID Numbers: NIH/NCI Grant #: R01 CA119903
Study First Received: March 6, 2007
Last Updated: August 19, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
Kaposi's sarcoma
KSHV
AIDS
HHV-8
treatment naive

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Sarcoma, Kaposi
Sarcoma
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Herpesviridae Infections
DNA Virus Infections
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Vascular Tissue
Protease Inhibitors
Ritonavir
Lopinavir
Reverse Transcriptase Inhibitors
Tenofovir
Tenofovir disoproxil
Efavirenz
Emtricitabine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 27, 2014