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Topical or Ablative Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Squamous Intraepithelial Lesions (ANCHOR)

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ClinicalTrials.gov Identifier: NCT02135419
Recruitment Status : Recruiting
First Posted : May 12, 2014
Last Update Posted : June 10, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
The Emmes Company, LLC
University of Arkansas
University of California, San Francisco
Information provided by (Responsible Party):
AIDS Malignancy Consortium

Tracking Information
First Submitted Date  ICMJE May 8, 2014
First Posted Date  ICMJE May 12, 2014
Last Update Posted Date June 10, 2019
Study Start Date  ICMJE September 24, 2014
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2014)
Time to anal cancer [ Time Frame: Time from randomization to diagnosis of anal cancer, assessed up to 5 years ]
The log-rank test will be used to compare the treatment and control arms with respect to time to detection of anal cancer. For each arm, the hazard rate and its 95% confidence interval will be estimated. The proportional hazards model will be used to assess the association of study site, lesion size, lesion location, nadir CD4 level and gender with time to detection of anal cancer.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02135419 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2014)
  • Incidence of adverse events for each treatment [ Time Frame: Up to 5 years ]
    Summarized by type of adverse event and severity grade for each of the treatments. For adverse events that occur in more than 5% of any of the treatments, the Poisson rates will be used to estimate the number of adverse events per unit time and the binomial proportion and its 95% confidence interval will be used to estimate the proportion of participants who reported the event.
  • Quality of life assessed using the Functional Assessment of Incontinence Therapy - Fecal (FAIT-F) questionnaire [ Time Frame: Up to 5 years ]
    Descriptive statistics will be used for subscales and scores for each arm and each time point. General estimating equations will be used to compare the two arms with respect to subscales and scores across time points and adjustment for intra-participant variability.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 8, 2014)
  • Viral factors in HSIL progression to cancer [ Time Frame: Up to 5 years ]
    Descriptive statistics will be used to describe the integration locus of HPV In the invasive cancers and whether they differ from those of the overlying HSIL. Descriptive statistics will also be used to determine if the loci differ in HSIL that have progressed and concurrent HSIL biopsies that did not progress. In each case only tissues that contain HPV 16 will be analyzed.
  • Host factors in HSIL progression to cancer [ Time Frame: Up to 5 years ]
    Linear models will be fitted for each gene. Moderated t-statistics, fold-change and the associated p values will be calculated for each gene. Since thousands of genes will be tested, false discovery rate (FDR)-adjusted values will be calculated using the Benjamini-Hochberg method. FDR values indicate the expected fraction of falsely declared differentially expressed (DE) genes among the total set of declared DE genes, i.e. FDR = 0.15 would indicate that 15% of the declared DE genes were expected to be false due to experimental noise instead of actual differential expression.
  • Host and viral biomarkers of progression from HSIL to cancer [ Time Frame: Up to 5 years ]
  • Behavioral risk factors for HSIL progression to cancer [ Time Frame: Up to 5 years ]
    For each risk factor of interest, Fisher's exact test or Pearson's chi-square test will be used to determine if there is an association. Factors associated with invasive anal cancer at the 0.10 significance level will be incorporated into a logistic regression model to determine if they are independently associated with invasive anal cancer. Cox regression analyses will also be used to evaluate the association between risk factors and time to diagnosis of invasive anal cancer.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Topical or Ablative Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Squamous Intraepithelial Lesions
Official Title  ICMJE ANCHOR Study: Anal Cancer/HSIL Outcomes Research Study
Brief Summary This randomized phase III trial compares topical or ablative treatment with active monitoring in preventing anal cancer in patients with human immunodeficiency virus (HIV) and high-grade squamous intraepithelial lesions (HSIL). Anal HSIL is tissue in the anal canal that has been damaged by infection with human papillomavirus (HPV) and is at risk for turning into anal cancer. It is not yet known if treating HSIL is more effective than active monitoring in preventing patients from developing anal cancer.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine the effectiveness of treating anal HSIL to reduce the incidence of anal cancer in human immunodeficiency virus (HIV)-infected men and women.

SECONDARY OBJECTIVES:

I. Determine safety of infrared coagulation, electrocautery, imiquimod, 85% trichloroacetic acid and 5-fluorouracil (fluorouracil) treatments for anal HSIL.

II. Compare quality of life measures between arms.

TERTIARY OBJECTIVES:

I. Determine the human papilloma virus (HPV) type in cancer and compare to that of overlying HSIL and HSIL biopsies collected concurrently that did not progress to cancer.

II. Determine the strain variant of HPV 16 in participants who progressed to anal cancer and compare to participants with HSIL biopsies who did not progress to cancer.

III. Determine the HPV integration site in overlying anal cancer to that of HSIL overlying the cancer and HSIL biopsies collected concurrently that did not progress to cancer.

IV. Perform gene expression array analysis comparing expression in anal cancer with HSIL overlying the cancer; perform gene expression array analysis comparing expression in HSIL biopsies that progressed to cancer with non-progressing HSIL biopsies at other locations; perform similar analyses comparing expression in HSIL biopsies that progressed to cancer with the same lesion at earlier time points prior to progression.

V. Characterize genetic changes in anal cancers compared with HSIL overlying the cancer; characterize genetic changes in HSIL biopsies that progressed to cancer compared with non-progressing HSIL biopsies at other locations; characterize genetic changes HSIL biopsies that progressed to cancer with the same lesion at earlier time points prior to progression.

VI. Identify host and viral biomarkers of progression from HSIL to cancer. VII. Evaluate medical history and behavioral risk factors for HSIL progression to cancer.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients are directed to receive either topical or ablative treatment at the discretion of the clinician. Patients receiving topical treatment apply imiquimod intra-anally, peri-anally or both thrice weekly for up to 16 weeks, fluorouracil twice daily for 5 days every 2 weeks for up to 16 weeks, or trichloroacetic acid every 3 weeks up to 12 weeks. Patients receiving ablative treatment using infrared coagulation, hyfrecation/electrocautery, or laser. Patients may undergo excision under anesthesia if the clinician believes none of the other treatment approaches will be effective. The number and timing of such treatments will be at the discretion of the investigator. Patients with persistent HSIL should continue a protocol-approved treatment or a new protocol treatment should be considered.

ARM II: Patients undergo active monitoring with examinations every 6 months. Every 12 months, patients undergo biopsies of visible lesions. Patients have cytology performed at every visit.

After completion of study treatment, patients are followed up every 6 months for up to 5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Anal Cancer
  • High-grade Squamous Intraepithelial Lesion
  • HIV Infection
  • Human Papilloma Virus Infection
Intervention  ICMJE
  • Drug: imiquimod
    Applied topically
    Other Names:
    • Aldara
    • IMQ
    • R 837
  • Drug: fluorouracil
    Applied topically
    Other Names:
    • 5-fluorouracil
    • 5-Fluracil
    • 5-FU
  • Device: infrared photocoagulation therapy
    Undergo infrared coagulation
    Other Names:
    • infrared coagulation
    • IRC
  • Device: thermal ablation therapy
    Undergo hyfrecation/electrocautery therapy
  • Device: laser therapy
    Undergo laser therapy
    Other Name: therapy, laser
  • Other: clinical observation
    Undergo active monitoring
    Other Name: observation
  • Other: laboratory biomarker analysis
    Correlative studies
Study Arms  ICMJE
  • Experimental: Arm I (treatment)
    Patients are directed to receive either topical or ablative treatment at the discretion of the clinician. Patients receiving topical treatment apply imiquimod intra-anally, peri-anally or both thrice weekly for up to 16 weeks, fluorouracil twice daily for 5 days every 2 weeks for up to 16 weeks, or trichloroacetic acid every 3 weeks up to 12 weeks. Patients receiving ablative treatment using infrared photocoagulation therapy, hyfrecation/electrocautery (thermal ablation therapy), or laser therapy. Patients may undergo excision under anesthesia if the clinician believes none of the other treatment approaches will be effective. The number and timing of such treatments will be at the discretion of the investigator. Patients with persistent HSIL should continue a protocol-approved treatment or a new protocol treatment should be considered. All participants will have samples collected for laboratory biomarker analysis.
    Interventions:
    • Drug: imiquimod
    • Drug: fluorouracil
    • Device: infrared photocoagulation therapy
    • Device: thermal ablation therapy
    • Device: laser therapy
    • Other: laboratory biomarker analysis
  • Active Comparator: Arm II (active monitoring)
    Patients undergo active monitoring with examinations for clinical observation every 6 months. Every 12 months, patients undergo biopsies of visible lesions. Patients have cytology sampling performed at every visit. All participants will have samples collected for laboratory biomarker analysis.
    Interventions:
    • Other: clinical observation
    • Other: laboratory biomarker analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 8, 2014)
5058
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2022
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • HIV-1 infection, as documented by any federally approved, licensed HIV test performed in conjunction with screening (or enzyme-linked immunosorbent assay [ELISA], test kit, and confirmed by western blot or other approved test); alternatively, this documentation may include a record that another physician has documented that the participant has HIV infection based on prior ELISA and western blot, or other approved diagnostic tests; an approved antibody test will be used to confirm diagnosis; if the physician is treating a patient with combination antiretroviral therapy (cART) with a history of HIV positivity based on an approved antibody test then repeat antibody confirmation is not necessary
  • No history of treatment or removal of HSIL
  • No history of anal cancer or signs of anal cancer at baseline, and no history of penile, vulvar, vaginal or cervical cancer
  • Biopsy-proven HSIL at baseline
  • At least one focus of HSIL must be identified that is not within a condyloma that may be treated after enrollment into the study
  • For females, cervical cytology (if having a cervix) and gynecologic evaluation including vulvar examination within 12 months prior to enrollment
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Life expectancy of greater than 5 years
  • Absolute neutrophil count: >= 750/mm^3
  • Platelets: >= 75,000/mm^3
  • Hemoglobin >= 9.0 g/dL
  • Women of childbearing potential must have a negative urine pregnancy test within 7 days of initiating study treatment if they have been randomized to the treatment arm; all women of childbearing potential must agree to use a reliable birth control method (oral contraceptive pills, intrauterine device, Nexplanon, DepoProvera, or permanent sterilization, etc., or another acceptable method as determined by the investigator) during the entire period of the trial (5 years), and must not intend to become pregnant during study participation and for 3 months after treatment is discontinued; all participants must be willing to comply with an acceptable birth control regimen as determined by the Investigator
  • Men randomized to the treatment arm should not father a baby while in this study; men who could father a child should use at least two forms of birth control for 3 months after stopping all study treatment
  • Ability to understand and the willingness to sign a written informed consent document
  • Participant is willing to be randomized and able to comply with the protocol
  • Clinician is comfortable with either following patient for up to 5 years without therapy or treating patient for up to 5 years

Exclusion Criteria:

  • Inability to provide informed consent
  • Patients who are receiving any other immunomodulatory investigational agents within the 4 weeks before randomization enrollment, other than investigational antiretroviral agents for HIV
  • History of anal cancer, penile, vulvar, vaginal or cervical cancer
  • History of prior treatment or removal of anal HSIL
  • Participant has symptoms related to HSIL and would benefit more from immediate treatment than from entry into the study and potential for randomization to active monitoring arm
  • Current systemic chemotherapy or radiation therapy that potentially causes bone marrow suppression that would preclude safe treatment of HSIL
  • History of HPV vaccination, or intention to receive an HPV vaccine during study participation
  • Prior pelvic radiation therapy that would preclude radiation therapy if anal cancer develops
  • Warts so extensive that they preclude the clinician from determining the extent and location of HSIL
  • Participant plans to relocate away from the study site during study participation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Abigail Arons, MPH 844-448-2888 abigail.arons@ucsf.edu
Contact: Jason Johnson Peretz, M.Phil 844-448-2888 jason.johnson2@ucsf.edu
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02135419
Other Study ID Numbers  ICMJE AMC-A01
NCI-2014-00636 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
AMC-A01 ( Other Identifier: AIDS - Associated Malignancies Clinical Trials Consortium )
AMC-A01 ( Other Identifier: CTEP )
U01CA121947 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AIDS Malignancy Consortium
Study Sponsor  ICMJE AIDS Malignancy Consortium
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • The Emmes Company, LLC
  • University of Arkansas
  • University of California, San Francisco
Investigators  ICMJE
Principal Investigator: Joel Palefsky, MD AIDS Malignancy Consortium
PRS Account AIDS Malignancy Consortium
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP