Clinical Trial: Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS)

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS)

Brief Summary: The purpose of this study is to determine whether Maraviroc is effective in the treatment of Kaposi's Sarcoma (KS), when it does not remit with standard antiretroviral drug therapy.

Detailed Summary:

Although the advent of antiretroviral therapy (ART) may have greatly decreased the incidence of Kaposi's Sarcoma (KS) in resource rich settings, KS continues to be the most prevalent AIDS-defining malignancy in the world and carries with it significant morbidity and mortality[1]. Indeed, in a recent epidemiological study examining cancers in Kampala, Uganda, KS was found to be second only to prostate cancer in terms of incidence rates[2].

There is growing evidence that CCR5 may be involved in the pathogenesis of KS. Kaposi's Sarcoma-associated Herpes Virus (KSHV), an agent found as necessary for KS pathogenesis [10, 11], encodes viral macrophage inflammatory proteins or vMIP [7-9]. vMIP-I and vMIP-II have been found to be ligands for chemokine receptors, and in particular the CCR5 receptor [5, 6], suggesting a potential role in the inflammatory process needed for KS pathogenesis. Further, vMIP-I induces Ca(2+) mobilization in monocytes expressing CCR5, suggesting an agonistic relationship between vMIP-I and the CCR5 receptor [4]. In addition, vMIP has been found to be proangiogenic when expressed in endothelial cells, a key feature of KS tumor survival [12]. As well, CCR5 has been found to be significantly increased in T cells populations of KS patients (from a preliminary study), and in 2 double-blind, placebo-controlled phase 3 studies in which a total of 1049 patients received the randomly assigned drug MVC, there was a trend revealing a lower incidence of KS in MVC arms vs placebo (0.36% vs 1.43%) [3]. This agonistic binding relationship between protein vMIP and CCR5, the proangiogenic activity associated with vMIP, the increased expression of CCR5 in KS, and trend towards lower incidence of KS when patients are taking MVC, suggest CCR5 may play an important role in KS pathogenesis. This involvement of CCR5 in KS pathogenesis implies that MVC may function as a potenti
Sponsor: University of California, San Francisco

Current Primary Outcome:

  • Change in Kaposi's Sarcoma Lesion Burden between Baseline and Week 1 [ Time Frame: Evaluations of the lesions will occur at baseline (week 0) and at week 1 ]
    The subjects' Kaposi's sarcoma related lesions will be evaluated during each visit for an increase or decrease in the number of lesions and whether the quality of the lesions show improvement or worsening of the condition.
  • Change in Kaposi's Sarcoma Lesion Burden between Baseline and Week 2 [ Time Frame: Evaluations of the lesions will occur at baseline (week 0) and at week 2 ]
    The subjects' Kaposi's sarcoma related lesions will be evaluated during each visit for an increase or decrease in the number of lesions and whether the quality of the lesions show improvement or worsening of the condition.
  • Change in Kaposi's Sarcoma Lesion Burden between Baseline and Week 4 [ Time Frame: Evaluations of the lesions will occur at baseline (week 0) and at week 4 ]
    The subjects' Kaposi's sarcoma related lesions will be evaluated during each visit for an increase or decrease in the number of lesions and whether the quality of the lesions show improvement or worsening of the condition.
  • Change in Kaposi's Sarcoma Lesion Burden between Baseline and Week 8 [ Time Frame: Evaluations of the lesions will occur at baseline (week 0) and at week 8 ]
    The subjects' Kaposi's sarcoma related lesions will be evaluated during each visit for an increase or decrease in the number of lesions and whether the quality of the lesions show improveme

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Effects of Maraviroc on CCR5 and KSHV levels in lesional skin. [ Time Frame: Week 0 (baseline), and week 96 or at the end of the therapy if it is discontinued early. ]
      A biopsy will be taken from the subjects' lesions at baseline and at the end of the study to determine whether there has been a change in CCR5 receptor levels or KSHV levels.
    • Change in CD4 count, and HIV viral load with Maraviroc from Baseline to Week 4 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 4. ]
      Blood samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in CD4 count or HIV viral load.
    • Change in CD4 count, and HIV viral load with Maraviroc from Baseline to Week 16 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 16. ]
      Blood samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in CD4 count or HIV viral load.
    • Change in CD4 count, and HIV viral load with Maraviroc from Baseline to Week 36 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 36. ]
      Blood samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in CD4 count or HIV viral load.
    • Change in CD4 count, and HIV viral load with Maraviroc from Baseline to Week 56 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 56. ]
      Blood samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in CD4 count or HIV viral load.
    • Change in CD4 count, and HIV viral load with Maraviroc from Baseline to Week 76 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 76. ]
      Blood samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in CD4 count or HIV viral load.
    • Change in CD4 count, and HIV viral load with Maraviroc from Baseline to Week 96 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 96. ]
      Blood samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in CD4 count or HIV viral load.
    • Effects on KSHV Viral Load with Maraviroc treatment from Baseline to Week 1 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline) and 1. ]
      Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.
    • Effects on KSHV Viral Load with Maraviroc treatment from Baseline to Week 2 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline) and 2. ]
      Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.
    • Effects on KSHV Viral Load with Maraviroc treatment from Baseline to Week 4 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline) and 4. ]
      Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.
    • Effects on KSHV Viral Load with Maraviroc treatment from Baseline to Week 16 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline) and 16. ]
      Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.
    • Effects on KSHV Viral Load with Maraviroc treatment from Baseline to Week 36 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline) and 36. ]
      Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.
    • Effects on KSHV Viral Load with Maraviroc treatment from Baseline to Week 56 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline) and 56. ]
      Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.
    • Same as current

      Information By: University of California, San Francisco

      Dates:
      Date Received: December 20, 2010
      Date Started: February 2011
      Date Completion: April 2015
      Last Updated: July 23, 2014
      Last Verified: July 2014