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Clinical Trials

MainTitle

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

This study is currently recruiting participants. (see Contacts and Locations)

Verified September 2017 by AIDS Malignancy Consortium

Sponsor
AIDS Malignancy Consortium

Collaborator
National Cancer Institute (NCI)
The EMMES Corporation
University of Arkansas
University of California, San Francisco

Information provided by (Responsible Party)
AIDS Malignancy Consortium
ClinicalTrials.gov Identifier
NCT02135419

First received: May 8, 2014
Last updated: September 1, 2017
Last Verified: September 2017
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
Anal Cancer
High-grade Squamous Intraepithelial Lesion
HIV Infection
Human Papilloma Virus Infection

Drug : imiquimod
Drug : fluorouracil
Procedure : infrared photocoagulation therapy
Procedure : thermal ablation therapy
Procedure : laser therapy
Other : clinical observation
Other : laboratory biomarker analysis
Procedure : quality-of-life assessment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: ANCHOR Study: Anal Cancer/HSIL Outcomes Research Study

Further study details as provided by AIDS Malignancy Consortium:

Primary Outcome Measures

  • 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.
Secondary Outcome Measures:
  • 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.
Other Outcome Measures:
  • 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.

Estimated Enrollment: 5058
Study Start Date: September 24, 2014
Estimated Study Completion Date: June 30, 2022
Estimated Primary Completion Date: June 30, 2022 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
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 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.
Drug: imiquimod

Applied topically

Other Name:
  • Aldara
  • IMQ
  • R 837

Drug: fluorouracil

Applied topically

Other Name:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU

Procedure: infrared photocoagulation therapy

Undergo infrared coagulation

Other Name:
  • infrared coagulation
  • IRC

Procedure: thermal ablation therapy

Undergo hyfrecation/electrocautery therapy

Procedure: laser therapy

Undergo laser therapy

Other Name: therapy, laser
Other: laboratory biomarker analysis

Correlative studies

Procedure: quality-of-life assessment

Ancillary studies

Other Name: quality of life assessment
Active Comparator: Arm II (active monitoring)
Patients undergo active monitoring with examinations every 6 months. Every 12 months, patients undergo biopsies of visible lesions. Patients have cytology sampling performed at every visit.
Other: clinical observation

Undergo active monitoring

Other Name: observation
Other: laboratory biomarker analysis

Correlative studies

Procedure: quality-of-life assessment

Ancillary studies

Other Name: quality of life assessment

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.

Eligibility

Eligibility

Ages Eligible for Study: 35 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

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

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02135419

Contacts

Contact:   Abigail Arons, MPH 844-448-2888 abigail.arons@ucsf.edu

Locations

United States, California
UCLA CARE Clinic Recruiting
Los Angeles, California, United States, 90035
Contact: Faith Landsman    310-557-3743    flandsman@mednet.ucla.edu
Principal Investigator: Ronald Mitsuyasu, MD
UCLA School of Nursing Recruiting
Los Angeles, California, United States, 90095
Contact: Dorothy Wiley, PhD    310-825-0540    dwiley@ucla.edu
Principal Investigator: Ronald Mitsuyasu, MD
Sub-Investigator: Ardis Moe, MD
University of California at San Francisco Anal Dysplasia Clinic Recruiting
San Francisco, California, United States, 94115
Contact: Rachel Silverstein    415-353-7443    rachel.silverstein@ucsf.edu
Principal Investigator: Joel Palefsky, MD
Sub-Investigator: J. Michael Berry-Lawhorn, MD
Sub-Investigator: Naomi Jay, RN, NP, PhD
United States, Colorado
University of Colorado Hospital Recruiting
Aurora, Colorado, United States, 80045
Contact: M. Ray, MSN    303-724-0712    graham.ray@ucdenver.edu
Principal Investigator: Thomas Campbell, MD
Sub-Investigator: Hillary Dunlevy, MD
Denver Public Health Recruiting
Denver, Colorado, United States, 80204
Contact: Jim Scott    303-602-8741    james.scott@dhha.org
Principal Investigator: Edward Gardener, MD
United States, District of Columbia
Capital Digestive Care Recruiting
Washington, D.C., District of Columbia, United States, 20006
Contact: Jessica Korman    240-737-0085    anchor@capitaldigestivecare.com
Principal Investigator: Jessica Korman, MD
Dupont Circle Physicians Group Recruiting
Washington, D.C., District of Columbia, United States, 20009
Contact: Benjamin Stearn, MD    202-745-0201    anchor@dupontdocs.com
Principal Investigator: Benjamin Stearn, MD
United States, Florida
ACC Clinic, Jackson Hospital Recruiting
Miami, Florida, United States, 33136
Contact: Isabella Rosa-Cunha    305-243-4598    irosa-cunha@med.miami.edu
Principal Investigator: Isabella Rosa-Cunha, MD
University of Miami Miller School of Medicine - Sylvester Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact: Isabella Rosa-Cunha    305-213-4713    isrosa-cunha@med.miami.edu
Principal Investigator: Isabella Rosa-Cunha, MD
United States, Illinois
Anal Dysplasia Clinic MidWest Recruiting
Chicago, Illinois, United States, 60614
Contact: Gary Bucher, MD    312-623-2625    garybuchermd@comcast.net
Principal Investigator: Gary Bucher, MD
United States, Louisiana
CrescentCare Health Recruiting
New Orleans, Louisiana, United States, 70119
Contact: Christiane Geisler    504-293-6878    Christiane.geisler@crescentcarehealth.org
Principal Investigator: Toby Fugate, DO
Sub-Investigator: Michael Hagensee, PhD
United States, Massachusetts
Boston Medical Center Recruiting
Boston, Massachusetts, United States, 02118
Contact: Elizabeth Stier, MD    617-414-5149    elizabeth.stier@bmc.org
Principal Investigator: Elizabeth Stier, MD
Fenway Health Terminated
Boston, Massachusetts, United States, 02215
United States, New York
Cornell Clinical Trials Unit, Chelsea Center Recruiting
New York, New York, United States, 10010
Contact: Christina Megill    212-746-7163    chm2029@med.cornell.edu
Principal Investigator: Timothy Wilkin, MD, MPH
Laser Surgery Care Recruiting
New York, New York, United States, 10011
Contact: Stephen Goldstone    212-242-6500    drgoldstone@lasersurgerycare.com
Principal Investigator: Stephen Goldstone, MD
Montefiore - Albert Einstein College of Medicine Recruiting
The Bronx, New York, United States, 10461
Contact: Zachary Thorogood    718-920-6680    zthorogo@montefiore.org
Principal Investigator: Rebecca Levine, MD
United States, North Carolina
Wake Forest Baptist Health Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Jin Zhang    336-716-4267    jinzhang@wakehealth.edu
Principal Investigator: Luis Barroso, MD
United States, Washington
Virginia Mason Medical Center Recruiting
Seattle, Washington, United States, 98101
Contact: Angie Woodstock    206-342-6539    angela.woodstock@virginiamason.org
Principal Investigator: David Aboulafia, MD
Harborview Medical Center Recruiting
Seattle, Washington, United States, 98104
Contact: Lindsay Legg    206-744-8748    lmlegg@u.washington.edu
Principal Investigator: Robert Harrington
The Polyclinic Recruiting
Seattle, Washington, United States, 98104
Contact: Gary Brown    206-860-4761    gary.brown@polyclinic.com
Principal Investigator: Juan De La Ossa, MD
Puerto Rico
University of Puerto Rico Recruiting
San Juan, Puerto Rico, 00936
Contact: Maribel Tirado-Gomez    787-772-8300    maribel.tirado1@upr.edu
Principal Investigator: Maribel Tirado-Gomez, MD

Sponsors and Collaborators

AIDS Malignancy Consortium
National Cancer Institute (NCI)
The EMMES Corporation
University of Arkansas
University of California, San Francisco

Investigators

Principal Investigator: Joel Palefsky, MD AIDS Malignancy Consortium
More Information

More Information


Responsible Party: AIDS Malignancy Consortium  
ClinicalTrials.gov Identifier: NCT02135419   History of Changes  
Other Study ID Numbers: AMC-A01  
  NCI-2014-00636  
  AMC-A01  
  AMC-A01  
  U01CA121947  
Study First Received: May 8, 2014  
Last Updated: September 1, 2017  

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Virus Diseases
Papilloma
Anus Neoplasms
Squamous Intraepithelial Lesions of the Cervix
Papillomavirus Infections
Fluorouracil
Imiquimod

ClinicalTrials.gov processed this data on October 20, 2017
This information is provided by ClinicalTrials.gov.