Clinical trial NCT00550589
Conditions: Anal Cancer Precancerous Condition
Keywords: high-grade squamous intraepithelial lesion stage 0 anal cancer
Sponsor: AIDS Malignancy Consortium
Start date: 2007-09-01; Completion date: 2010-02-01
Enrollment: 33 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Arms: arm 1: 1.0% topical cidofovir cream
Interventions: intervention 1: cidofovir intervention 2: DNA methylation analysis intervention 3: gene expression analysis intervention 4: polymerase chain reaction intervention 5: biopsy intervention 6: histopathologic examination
Intervention descriptions: intervention 1: 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. intervention 2: formalin fixed biopsy collected at baseline and 6 weeks after treatment discontinuation intervention 3: punch biopsy collected at baseline, after cycle 1, and 6 weeks after treatment discontinuation intervention 4: performed on punch biopsy specimens collected at baseline, after cycle 1, and 6 weeks after treatment discontinuation intervention 5: punch biopsy collected at baseline, after cycle 1, and 6 weeks after treatment discontinuation intervention 6: Evaluated at baseline and 6 weeks after treatment discontinuation

Protocol documents: