Cidofovir in Treating HIV-Infected Patients With High-Grade Squamous Intraepithelial Lesions of the Skin Near the Anus

NCT00550589 | Completed Phase 2 Results

• 3 other identifiers: AMC-046U01CA121947CDR0000570720
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 8

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.

Conditions

Anal Cancer; Precancerous Condition

Keywords

high-grade squamous intraepithelial lesion; stage 0 anal cancer

Outcome Measures

Primary Outcomes (2)

• Proportion of Patients With Regression of Perianal High-grade Squamous Intraepithelial Lesions (HSIL)

  6 weeks after treatment discontinuation

• Safety and Tolerability of Topical Cidofovir as Assessed by NCI CTCAE v3.0

  Number of study patients who had a serious adverse event

  Every 2 weeks on study, 6 weeks after treatment discontinuation

Secondary Outcomes (6)

• Human Papilloma Virus (HPV) DNA Type in Perianal HSIL and Normal Perianal Tissue

  Baseline

• Correlation of Clinical Regression of Perianal HSIL With Clearance of HPV DNA

  6 weeks after treatment discontinuation

• Identification of HPV-DNA Types Present in the Anus

  Baseline

• Identification of Abnormally Methylated Genes in Perianal Dysplasia

  Baseline, after cycle 1, and 6 weeks after treatment discontinuation

• Distribution of Abnormally Methylated Genes Among HSIL, Low-grade Squamous Intraepithelial Lesions, and Normal Perianal Skin

  Baseline, after cycle 1, and 6 weeks after treatment discontinuation

Study Arms (1)

Cidofovir

EXPERIMENTAL

1.0% topical cidofovir cream

Drug: cidofovir; Genetic: DNA methylation analysis; Genetic: gene expression analysis; Genetic: polymerase chain reaction; Procedure: biopsy; Procedure: histopathologic examination

Interventions

cidofovir DRUG

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.

Cidofovir

DNA methylation analysis GENETIC

formalin fixed biopsy collected at baseline and 6 weeks after treatment discontinuation

Cidofovir

gene expression analysis GENETIC

punch biopsy collected at baseline, after cycle 1, and 6 weeks after treatment discontinuation

Cidofovir

polymerase chain reaction GENETIC

performed on punch biopsy specimens collected at baseline, after cycle 1, and 6 weeks after treatment discontinuation

Cidofovir

biopsy PROCEDURE

punch biopsy collected at baseline, after cycle 1, and 6 weeks after treatment discontinuation

Cidofovir

histopathologic examination PROCEDURE

Evaluated at baseline and 6 weeks after treatment discontinuation

Cidofovir

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• AIDS Malignancy Consortium: lead
• National Cancer Institute (NCI): collaborator
• The Emmes Company, LLC: collaborator

Study Sites (8)

UCLA Clinical AIDS Research and Education (CARE) Center

Los Angeles, California, 90095-1793, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Boston University Cancer Research Center

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Laser Surgery Care

New York, New York, 10010, United States

Location

New York Weill Cornell Cancer Center at Cornell University

New York, New York, 10021, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Benaroya Research Institute at Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Related Publications (1)

• 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.

  PMID: 23032420 RESULT

MeSH Terms

Conditions

Anus Neoplasms; Precancerous Conditions; Squamous Intraepithelial Lesions

Interventions

Cidofovir; DNA Methylation; Gene Expression Profiling; Polymerase Chain Reaction; Biopsy

Condition Hierarchy (Ancestors)

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases; Morphological and Microscopic Findings; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Cytosine; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Methylation; Alkylation; Biochemical Phenomena; Chemical Phenomena; Metabolism; Genetic Phenomena; Genetic Techniques; Investigative Techniques; Nucleic Acid Amplification Techniques; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Results Point of Contact

• Title: Jeannette Lee
• Organization: Statistical Center of AIDS Malignancy Consortium

jylee@uams.edu

(501) 526-6712

Study Officials

• Elizabeth Stier, MD

  Boston Medical Center

  STUDY CHAIR

• Joel Palefsky, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2007
• First Posted: October 30, 2007
• Study Start: September 1, 2007
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: December 21, 2015
• Results First Posted: June 22, 2011

Record last verified: 2015-11

Locations

US (8)