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Anal CancerPhase 2NCT00550589

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

A Phase 2 study testing cidofovir, DNA methylation analysis and gene expression analysis in people with Anal Cancer and Precancerous Condition, run by AIDS Malignancy Consortium at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Anal Cancer, Precancerous Condition
What is being tested?
cidofovir, DNA methylation analysis and gene expression analysis
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
8 sitesUnited States
Study dates
Sep 2007to Feb 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Boston University Cancer Research Center

    Boston, Massachusetts, 02118

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • UCLA Clinical AIDS Research and Education (CARE) Center

    Los Angeles, California, 90095-1793

  • Laser Surgery Care

    New York, New York, 10010

  • New York Weill Cornell Cancer Center at Cornell University

    New York, New York, 10021

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94115

  • Benaroya Research Institute at Virginia Mason Medical Center

    Seattle, Washington, 98101

  • Montefiore Medical Center

    The Bronx, New York, 10461

Other trials in United States

About this study

Official title: Phase IIA Trial of 1% Topical Cidofovir for Treatment of High-Grade Perianal Squamous Intraepithelial Lesions in HIV-Infected Men and Women

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.

Read the 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.

Being tested
cidofovir, DNA methylation analysis, gene expression analysis, polymerase chain reaction, biopsy
Keywords
high-grade squamous intraepithelial lesion, stage 0 anal cancer
Medical subject headings
Anus Neoplasms, Precancerous Conditions, Squamous Intraepithelial Lesions

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cidofovirDrug

    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 analysisGenetic

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

  • gene expression analysisGenetic

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

  • polymerase chain reactionGenetic

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

  • biopsyProcedure or surgery

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

  • histopathologic examinationProcedure or surgery

    Evaluated at baseline and 6 weeks after treatment discontinuation

Study groups in NCT00550589
Study groupRoleWhat they receive
CidofovirExperimental1.0% topical cidofovir cream
Receives: Drug: cidofovir; Genetic: DNA methylation analysis; Genetic: gene expression analysis; Genetic: polymerase chain reaction; Procedure: biopsy; Procedure: histopathologic examination

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 6 weeks after treatment discontinuation

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

    Number of study patients who had a serious adverse event

    Measured: Every 2 weeks on study, 6 weeks after treatment discontinuation

Secondary outcomes (6)

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

    Number of patients with HPV16 at baseline in perianal HSIL and normal perianal tissue

    Measured: Baseline

  2. Correlation of Clinical Regression of Perianal HSIL With Clearance of HPV DNA

    Number of patients who cleared HPV among those who had a complete or partial response

    Measured: 6 weeks after treatment discontinuation

  3. Identification of HPV-DNA Types Present in the Anus

    Number of patients with HPV16 type present in the anus from anal swab or cytobrush at baseline

    Measured: Baseline

  4. Identification of Abnormally Methylated Genes in Perianal Dysplasia

    Identification of abnormally methylated genes in perianal dysplasia

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

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

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

  6. Changes in Gene Expression in Perianal HSIL After Exposure to Cidofovir as Assessed by RNA Microarray Analysis

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Oct 2007 (estimated)
  2. Study startSep 2007
  3. Primary completionFeb 2010
  4. Study completionFeb 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00550589
Sponsor's protocol ID
AMC-046
Other IDs
U01CA121947, CDR0000570720
Status last verified
Nov 2015
First submitted
26 Oct 2007
Last updated
21 Dec 2015
Data monitoring committee
No

Publications

  • 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.

    PubMed 23032420

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing cidofovir, DNA methylation analysis and gene expression analysis in people with Anal Cancer and Precancerous Condition, run by AIDS Malignancy Consortium at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jun 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Patients With Regression of Perianal High-grade Squamous Intraepithelial Lesions (HSIL) (time frame: 6 weeks after treatment discontinuation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00550589, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2015.

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