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
Intervention: cidofovir; DNA methylation analysis; gene expression analysis; polymerase chain reaction; biopsy; histopathologic examination
Intervention description: 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
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: high-grade squamous intraepithelial lesion; stage 0 anal cancer

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.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed perianal high-grade squamous intraepithelial lesions (HSIL)
             within the past 12 weeks

               -  The perianal skin (i.e., perianus) is defined as extending radially 5 cm from the
                  anal verge

               -  Lesions must cover a surface area of ≥ 3 square centimeters

               -  Lesions extending outside the perianus (e.g., vulvar lesions on the posterior
                  perineum bordering the perianus) are allowed

          -  Serologic documentation of HIV infection AND meets 1 of the following criteria:

               -  Has been on stable highly active anti-retroviral therapy (HAART) for ≥ 12 weeks
                  prior to study entry

               -  Has a CD4 count of > 200/mm³ AND is not receiving anti-retroviral therapy OR is
                  currently receiving a non-HAART* anti-retroviral regimen with no plans to
                  initiate HAART within the next 12 weeks NOTE: * A non-HAART regimen is considered
                  to be a therapy that does not include a protease inhibitor or a non-nucleoside
                  reverse transcriptase inhibitor

          -  No untreated invasive cancer of the lower genital tract

          -  No concurrent neoplasia requiring cytotoxic therapy

        PATIENT CHARACTERISTICS:

          -  Karnofsky performance status 70-100%

          -  Life expectancy ≥ 3 months

          -  Hemoglobin ≥ 8 g/dL

          -  ANC ≥ 1,000/mm³

          -  Platelet count ≥ 75,000/mm³

          -  Creatinine < 1.5 times upper limit of normal (ULN)

          -  Total or conjugated (direct) bilirubin ≤ 2.5 times ULN

          -  AST and ALT ≤ 3 times ULN

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for 3 months after
             completion of study therapy

          -  No acute, opportunistic infection other than oral thrush, yeast vaginitis, or genital
             herpes within the past 14 days

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  Recovered from prior ablative or surgical treatment of perianal dysplasia

          -  At least 4 weeks since prior topical treatment for perianal dysplasia

               -  If any prior treatment caused significant trauma to ther area, healing should
                  occur prior to starting treatment

          -  More than 14 days since prior acute treatment for infection (other than for oral
             thrush, yeast vaginitis, or genital herpes) or other serious medical illness

          -  No concurrent corticosteroids other than replacement doses

          -  No other concurrent investigational drugs except IND-approved anti-retroviral agents

          -  No concurrent systemic cytotoxic chemotherapy