Cidofovir in Treating HIV-Infected Patients With High-Grade Squamous Intraepithelial Lesions of the Skin Near the Anus
Condition: Anal Cancer; Precancerous Condition
MeSH terms: Anus Neoplasms; Precancerous Conditions; Squamous Intraepithelial Lesions of the Cervix
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: High-grade squamous intraepithelial lesions of the skin near the anus are caused
      by the human papillomavirus (HPV). Antiviral drugs,, such as cidofovir, act against viruses
      and may stop these lesions from becoming cancer.

      PURPOSE: This phase II trial is studying the side effects and how well topical cidofovir
      works in treating HIV-infected patients with high-grade squamous intraepithelial lesions of
      the skin near the anus.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To evaluate the safety and tolerability of topical cidofovir in HIV-infected patients
           with perianal high-grade squamous intraepithelial lesions (HSIL).

        -  To estimate the regression rate of perianal HSIL in patients treated with this regimen.

      Secondary

        -  To determine the human papilloma virus (HPV) DNA types and HPV strain variants present
           in perianal HSIL and normal perianal tissue.

        -  To determine if clinical regression of perianal HSIL is associated with clearance of HPV
           DNA.

        -  To identify the HPV DNA types present in the anus and cervix and compare them with the
           HPV DNA present in the perianus in order to determine if the HPV types associated with
           the perianal lesions are the same as those infecting the anus and cervix.

        -  To determine if there are abnormally methylated genes in perianal HSIL compared with
           normal perianal tissue and if these genes are the same or different from those that have
           been previously identified in anal and cervical dysplasia.

        -  To determine whether methylated genes are changed after treatment with cidofovir.

        -  To characterize differences in gene expression in perianal HSIL compared with normal
           perianal tissue.

        -  To examine changes in gene expression in perianal HSIL after exposure to cidofovir using
           RNA microarray analysis and confirm results with real-time polymerase chain reaction.

        -  To correlate pretreatment CD4 count, viral load, lesion size, methylation pattern,
           and/or HPV type and strain with the clinical efficacy of topical cidofovir.

      OUTLINE: This is a multicenter study.

      Patients apply topical cidofovir to the perianus once daily on days 1-5. Patients undergo
      punch biopsy of pretreatment lesional biopsy sites on day 14. Beginning 2-4 weeks after
      biopsy, patients receive course 2 of cidofovir therapy. Subsequent treatment repeats every 14
      days for up to 6 courses* in the absence of disease progression or unacceptable toxicity.

      NOTE: *Patients receive a total of 6 courses of study therapy.

      Patients undergo collection of tumor and normal tissue for histopathological and molecular
      correlative studies. Punch biopsies are obtained at baseline, after the first course of
      therapy, and at 6 weeks after completion of therapy. Tissue samples are examined for
      histopathology, human papilloma virus (HPV)DNA typing, DNA methylation, and gene expression
      (via RNA microarray analysis and polymerase chain reaction).

      After completion of study therapy, patients are followed at 6 weeks.
    

Intervention name(s): cidofovir; DNA methylation analysis; gene expression analysis; polymerase chain reaction; biopsy; histopathologic examination
Intervention type(s): Drug; Genetic; Genetic; Genetic; Procedure; Procedure
Intervention description(s): 1.0% topical cream self-applied once daily for 5 consecutive days, with no treatment for the remaining 9 days (a treatment cycle). Subjects will receive up to 6 cycles of treatment.; formalin fixed biopsy collected at baseline and 6 weeks after treatment discontinuation; punch biopsy collected at baseline, after cycle 1, and 6 weeks after treatment discontinuation; performed on punch biopsy specimens collected at baseline, after cycle 1, and 6 weeks after treatment discontinuation; punch biopsy collected at baseline, after cycle 1, and 6 weeks after treatment discontinuation; Evaluated at baseline and 6 weeks after treatment discontinuation
Intervention MeSH terms: Cidofovir
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: high-grade squamous intraepithelial lesion; stage 0 anal cancer