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

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Status: Active

Description

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.

Eligibility Criteria

Inclusion Criteria

  • HIV positive; documentation of HIV-1 infection by means of any one of the following: * Documentation of HIV diagnosis in the medical record by a licensed health care provider; * Documentation of receipt of antiretroviral therapy (ART) by a licensed health care provider (documentation may be a record of an ART prescription in the participant’s medical record, a written prescription in the name of the participant for ART, or pill bottles for ART with a label showing the participant’s name; receipt of at least two agents is required; each component agent of a multi-class combination ART regimen will be counted toward the 2-agent requirement, excepting receipt of a pre-exposure prophylaxis [PrEP] regimen alone [e.g., Truvada], which is exclusionary); * HIV-1 ribonucleic acid (RNA) detection by a licensed HIV-1 RNA assay demonstrating > 1000 RNA copies/mL; * Any licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 western blot confirmation or HIV rapid multispot antibody differentiation assay * NOTE: A “licensed” assay refers to a United States (US) Food and Drug Administration (FDA)-approved assay, which is required for all investigational new drug (IND) studies
  • Biopsy-proven anal HSIL at baseline (anal intraepithelial neoplasia [AIN]2 with a positive cyclin-dependent kinase inhibitor 2A [p16] stain, AIN2-3, or AIN3)
  • 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, documentation that the participant is being followed with cervical cytology and/or HPV testing per current “Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents” and American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines; cervical cytology must be performed prior to enrollment for women who are overdue for screening per the guidelines; women should also have confirmation of absence of cancer or suspected cancer upon visual examination of the vulva, vagina, and cervix 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 (FCBP) must have a negative urine pregnancy test within 7 days prior to randomization enrollment; female participants enrolled in the treatment arm are advised to not become pregnant during study participation; all women of childbearing potential must agree to either commit to continued abstinence from heterosexual intercourse or to use a reliable birth control method during heterosexual intercourse (oral contraceptive pills, intrauterine device, Nexplanon, DepoProvera, or bilateral tubal ligation, etc., or another acceptable method as determined by the investigator) during the entire period of the trial (5 years or more), and must not intend to become pregnant during study participation and for 3 months after treatment is discontinued if the participant is enrolled in the treatment arm; female participants, if engaging in heterosexual intercourse, 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 receiving topical treatment during this study; men who could father a child must agree to use at least one form of birth control during or continued abstinence from heterosexual intercourse if receiving topical treatment during the study, and for 2 weeks after stopping topical treatment
  • Participant is willing to be randomized and able to comply with the protocol
  • Clinician is comfortable that cancer has adequately been ruled out and is willing to follow the participant for up to 5 years without treatment of the HSIL

Exclusion Criteria

  • Participant is unable to provide informed consent
  • Participants who received any other chronic (defined as more than 50% of the time in the last 6 months) systemic immunomodulatory agents (replacement doses of steroids for adrenal insufficiency are permitted or treatment with prednisone =< 5 mg/day) or investigational agents within the 4 weeks before randomization enrollment, other than investigational antiretroviral agents for HIV and investigational or approved agents for hepatitis C
  • History of anal cancer, penile, vulvar, vaginal, or cervical cancer, or signs of any of these malignancies at baseline; participants with prior carcinoma in situ will not be considered to have prior cancer for eligibility purposes
  • 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
  • Participants who only have a single HSIL lesion that is likely to be removed entirely with the initial screening biopsy
  • 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 to a location that does not have an Anal Cancer/HSIL Outcomes Research (ANCHOR) study site during study participation

Locations & Contacts

California

Los Angeles
UCLA Center for Clinical AIDS Research and Education
Status: Active
Contact: Faith Landsman
Phone: 310-557-3743 Email: flandsman@mednet.ucla.edu
San Francisco
UCSF Medical Center-Mount Zion
Status: Active
Contact: Joel Palefsky
Phone: 415-476-1574 Email: jpalefsky@medicine.ucsf.edu

Colorado

Denver
Denver Metro Health Clinic and Outreach Services
Status: Active
Contact: James Scott
Phone: 303-602-8741 Email: james.scott@dhha.org

District of Columbia

Washington
Dupont Circle Physicians Group PC
Status: Active
Contact: Benjamin Franklin Stearn
Phone: 202-745-0201 Email: anchor@dupontdocs.com
Metropolitan Gastroenterology Group
Status: Active
Contact: Joel Palefsky
Phone: 877-827-3222

Florida

Miami
Jackson Memorial Hospital-Holtz Children's Hospital
Status: Active
Contact: Joel Palefsky
Phone: 877-827-3222
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: Active
Contact: Isabella Rosa-Cunha
Phone: 305-243-4598 Email: irosa-cunha@med.miami.edu

Georgia

Atlanta
Grady Health System
Status: Active
Contact: Joel Palefsky
Phone: 877-827-3222

Illinois

Chicago
Anal Dysplasia Clinic MidWest
Status: Active
Contact: Gary G. Bucher
Phone: 312-623-2625 Email: garybuchermd@comcast.net

Louisiana

New Orleans
Louisiana State University Health Science Center
Status: Active
Contact: Joel Palefsky
Phone: 415-476-1574 Email: jpalefsky@medicine.ucsf.edu

Massachusetts

Boston
Boston Medical Center
Status: Active
Contact: Elizabeth A. Stier
Phone: 617-414-5149 Email: elizabeth.stier@bmc.org
The Fenway Institute
Status: Active
Contact: Lori Ann Panther
Phone: 617-632-7706 Email: lpanther@didmc.harvard.edu

New York

Bronx
Montefiore Medical Center - Moses Campus
Status: Active
Contact: Mark H. Einstein
Phone: 973-972-5266 Email: Mark.Einstein@Rutgers.edu
Montefiore Medical Center-Einstein Campus
Status: Active
Contact: Mark H. Einstein
Phone: 973-972-5266 Email: Mark.Einstein@Rutgers.edu
New York
Cornell Clinical Trials Unit
Status: Active
Contact: Timothy James Wilkin Email: tiw2001@med.cornell.edu
Laser Surgery Care
Status: Active
Contact: Stephen Elliot Goldstone
Phone: 212-242-6500 Email: drgoldstone@lasersurgerycare.com

North Carolina

Winston-Salem
Wake Forest University Health Sciences
Status: Active
Contact: Luis Francis Barroso
Phone: 336-716-8918 Email: lbarroso@wakehealth.edu

Puerto Rico

San Juan
University of Puerto Rico
Status: Active
Contact: Maribel Tirado-Gomez
Phone: 787-772-8300ext1108 Email: maribel.tirado1@upr.edu

Washington

Seattle
Harborview Medical Center
Status: Active
Contact: Lindsay Legg
Phone: 206-744-8748 Email: lmlegg@u.washington.edu
The Polyclinic - Broadway
Status: Active
Contact: Gary T. Brown
Phone: 206-860-4761 Email: gary.brown@polyclinic.com
The Polyclinic Madison Center
Status: Active
Contact: Gary T. Brown
Phone: 206-860-4761 Email: gary.brown@polyclinic.com
Virginia Mason Medical Center
Status: Active
Contact: Angie Woodstock
Phone: 206-342-6539 Email: angela.woodstock@virginiamason.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine whether treating anal HSIL is effective in reducing the incidence of anal cancer in HIV-infected men and women.

SECONDARY OBJECTIVES:

I. To determine the safety of infrared coagulation, electrocautery, imiquimod, laser, and 5-fluorouracil (fluorouracil) treatments for anal HSIL.

TERTIARY OBJECTIVES:

I. Determine the 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 or fluorouracil twice daily for 5 days every 2 weeks for up to 16 weeks. Patients receiving ablative treatment undergo 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. At the final study visit, patients undergo biopsy of all visible lesions or a random 4-quadrant biopsy if no lesions are seen.

All participants will be followed up to 5 years after the last participant’s date of randomization, diagnosis of invasive anal cancer, or until death, whichever occurs first.

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
AIDS Malignancy Consortium

Principal Investigator
Joel Palefsky

Trial IDs

Primary ID AMC-A01
Secondary IDs NCI-2014-00636
Clinicaltrials.gov ID NCT02135419