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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2015 by AIDS Malignancy Consortium
National Cancer Institute (NCI)
The EMMES Corporation
University of Arkansas
University of California, San Francisco
Information provided by (Responsible Party):
AIDS Malignancy Consortium Identifier:
First received: May 8, 2014
Last updated: October 2, 2015
Last verified: September 2015
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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: ANCHOR Study: Anal Cancer/HSIL Outcomes Research Study

Resource links provided by NLM:

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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Behavioral risk factors for HSIL progression to cancer [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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 2014
Estimated Study Completion Date: June 2022
Estimated Primary Completion Date: June 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 Names:
  • Aldara
  • IMQ
  • R 837
Drug: fluorouracil
Applied topically
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Procedure: infrared photocoagulation therapy
Undergo infrared coagulation
Other Names:
  • 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

  Show Detailed Description


Ages Eligible for Study:   35 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
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 identifier: NCT02135419

United States, California
UCLA CARE Clinic Not yet recruiting
Los Angeles, California, United States, 90035
Contact: Faith Landsman    310-557-3743   
Principal Investigator: Ronald Mitsuyasu, MD         
University of California at San Francisco Anal Dysplasia Clinic Recruiting
San Francisco, California, United States, 94115
Contact: Rachel Silverstein    415-353-7443   
Principal Investigator: Joel Palefsky, MD         
Sub-Investigator: J. Michael Berry-Lawhorn, MD         
Sub-Investigator: Naomi Jay, RN, NP, PhD         
United States, Illinois
Anal Dysplasia Clinic MidWest Recruiting
Chicago, Illinois, United States, 60614
Contact: Gary Bucher, MD    312-623-2625   
Principal Investigator: Gary Bucher, MD         
United States, Massachusetts
Boston Medical Center Recruiting
Boston, Massachusetts, United States, 02118
Contact: Elizabeth Stier, MD    617-414-5149   
Principal Investigator: Elizabeth Stier, MD         
Fenway Health Recruiting
Boston, Massachusetts, United States, 02215
Contact: Mayeso Chithambo    617-927-6348   
Principal Investigator: Lori Panther, MD         
United States, New York
Hutchinson Metro Center Ambulatory Care Center Recruiting
Bronx, New York, United States, 10461
Contact: Marisol Rivera    718-405-8200 ext 8397   
Principal Investigator: Mark Einstein, MD, MS         
Montefiore Medical Center Clinical Trials and Research Unit Recruiting
Bronx, New York, United States, 10461
Contact: Marisol Rivera    718-405-8200 ext 8397   
Principal Investigator: Mark Einstein, MD, MS         
Cornell Clinical Trials Unit, Chelsea Center Recruiting
New York, New York, United States, 10010
Contact: Christina Megill    212-746-7163   
Principal Investigator: Timothy Wilkin, MD, MPH         
Laser Surgery Care Recruiting
New York, New York, United States, 10011
Contact: Stephen Goldstone    212-242-6500   
Principal Investigator: Stephen Goldstone, MD         
United States, North Carolina
Wake Forest Baptist Health Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Melissa Trader    336-716-8918   
Principal Investigator: Luis Barroso, MD         
Sponsors and Collaborators
AIDS Malignancy Consortium
National Cancer Institute (NCI)
The EMMES Corporation
University of Arkansas
University of California, San Francisco
Principal Investigator: Joel Palefsky, MD AIDS Malignancy Consortium
  More Information

Responsible Party: AIDS Malignancy Consortium 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: October 2, 2015
Health Authority: United States: Food and Drug Administration
United States: Federal Government
United States: Institutional Review Board
United States: Data and Safety Monitoring Board

Additional relevant MeSH terms:
Anus Neoplasms
Communicable Diseases
Papillomavirus Infections
Squamous Intraepithelial Lesions of the Cervix
Virus Diseases
Anus Diseases
Colorectal Neoplasms
DNA Virus Infections
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Genital Diseases, Female
Intestinal Diseases
Intestinal Neoplasms
Neoplasms by Site
Precancerous Conditions
Rectal Diseases
Rectal Neoplasms
Skin Diseases
Skin Diseases, Infectious
Skin Diseases, Viral
Tumor Virus Infections
Uterine Cervical Diseases
Uterine Cervical Dysplasia
Uterine Diseases
Fluorouracil processed this record on May 30, 2016