Cidofovir in Treating HIV-Infected Patients With High-Grade Squamous Intraepithelial Lesions of the Skin Near the Anus
NCT ID: NCT00550589
Last Updated: 2015-12-21
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
33 participants
INTERVENTIONAL
2007-09-30
2010-02-28
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Cidofovir
1.0% topical cidofovir cream
cidofovir
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.
DNA methylation analysis
formalin fixed biopsy collected at baseline and 6 weeks after treatment discontinuation
gene expression analysis
punch biopsy collected at baseline, after cycle 1, and 6 weeks after treatment discontinuation
polymerase chain reaction
performed on punch biopsy specimens collected at baseline, after cycle 1, and 6 weeks after treatment discontinuation
biopsy
punch biopsy collected at baseline, after cycle 1, and 6 weeks after treatment discontinuation
histopathologic examination
Evaluated at baseline and 6 weeks after treatment discontinuation
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
cidofovir
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.
DNA methylation analysis
formalin fixed biopsy collected at baseline and 6 weeks after treatment discontinuation
gene expression analysis
punch biopsy collected at baseline, after cycle 1, and 6 weeks after treatment discontinuation
polymerase chain reaction
performed on punch biopsy specimens collected at baseline, after cycle 1, and 6 weeks after treatment discontinuation
biopsy
punch biopsy collected at baseline, after cycle 1, and 6 weeks after treatment discontinuation
histopathologic examination
Evaluated at baseline and 6 weeks after treatment discontinuation
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
18 Years
120 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
The Emmes Company, LLC
INDUSTRY
AIDS Malignancy Consortium
NETWORK
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Elizabeth Stier, MD
Role: STUDY_CHAIR
Boston Medical Center
Joel Palefsky, MD
Role: PRINCIPAL_INVESTIGATOR
University of California, San Francisco
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
UCLA Clinical AIDS Research and Education (CARE) Center
Los Angeles, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
Boston University Cancer Research Center
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Laser Surgery Care
New York, New York, United States
New York Weill Cornell Cancer Center at Cornell University
New York, New York, United States
Montefiore Medical Center
The Bronx, New York, United States
Benaroya Research Institute at Virginia Mason Medical Center
Seattle, Washington, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Stier EA, Goldstone SE, Einstein MH, Jay N, Berry JM, Wilkin T, Lee JY, Darragh TM, Da Costa M, Panther L, Aboulafia D, Palefsky JM. Safety and efficacy of topical cidofovir to treat high-grade perianal and vulvar intraepithelial neoplasia in HIV-positive men and women. AIDS. 2013 Feb 20;27(4):545-51. doi: 10.1097/QAD.0b013e32835a9b16.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
CDR0000570720
Identifier Type: OTHER
Identifier Source: secondary_id
AMC-046
Identifier Type: -
Identifier Source: org_study_id