Anti-Retrovirals for Kaposi's Sarcoma

NCT00444379 | Completed Phase 4 DMC

• 1 other identifier: NIH/NCI Grant #: R01 CA119903
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Kaposi's Sarcoma; HIV Infections

Keywords

Kaposi's sarcoma; KSHV; AIDS; HHV-8; treatment naive

Outcome Measures

Primary Outcomes (1)

• 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)

Study Arms (2)

PI-based HAART regimen

ACTIVE COMPARATOR

PI-based HAART regimen (lopinavir/ritonavir plus emtricitabine/tenofovir)

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)

Drug: Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovir

Interventions

Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovir DRUG

Lopinavir/ritonavir 200/50mg plus Emtricitabine/Tenofovir 200/300mg versus Efavirenz 600mg plus Emtricitabine/Tenofovir 200/300mg

Also known as: Lopinavir/ritonavir Aluvia (ALUABT), Efavirenz Stocrin (EFVBMM), Emtricitabine/Tenofovir Truvada (TRUGLD)

PI-based HAART regimen; non-nucleoside reverse transcriptase inhibitor

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institutes of Health (NIH): collaborator
• Gilead Sciences: collaborator
• Abbott: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Infectious Diseases Institute, Mulago Hospital

Kampala, Uganda

Location

Related Links

• Medline Plus- Health Information

MeSH Terms

Conditions

Sarcoma, Kaposi; HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Lopinavir; Ritonavir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Tenofovir; Organophosphonates; Organophosphorus Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Dr. Jeffrey N Martin, MD, MPH

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Dr. Edward K Mbidde, MBChB, MMed

  MRC/UVRI and LSHTM Uganda Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2007
• First Posted: March 7, 2007
• Study Start: April 1, 2007
• Primary Completion: February 1, 2012
• Study Completion: July 1, 2012
• Last Updated: August 20, 2014

Record last verified: 2014-08

Locations

UG (1)