Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Lesions

NCT02135419 | Completed Phase 3 Results DMC FDA Drug FDA Device

• 5 other identifiers: AMC-A01NCI-2014-00636U01CA121947UM1CA121947ANCHOR
• Study Type: interventional
• Target: 4,446
• Locations: 2 countries
• Sites: 25

Brief Summary

The randomized phase of the trial compared 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. The ANCHOR Data Safety Monitoring Board (DSMB) determined that the primary study endpoint was completed, based on the data and statistical analysis presented to them on 07SEP2021. In the post-randomization phase of this trial, all enrolled participants are offered treatment for HSIL and/or follow-up, at the participant's choice.

Conditions

Anal Cancer; High-grade Squamous Intraepithelial Lesion; HIV Infection; Human Papilloma Virus Infection

Keywords

anal cancer; high-grade squamous intraepithelial lesion; anal HSIL; HIV; HIV/AIDS; human papillomavirus; HPV

Outcome Measures

Primary Outcomes (1)

• Anal Cancer Incidence

  Anal cancer incidence is calculated as the number of anal cancer cases detected per 100,000 person years

  Time from randomization to diagnosis of anal cancer, assessed up to 5 years post randomization

Secondary Outcomes (2)

• Incidence of Adverse Events for Each Treatment

  Up to 5 years after randomization

• Change in Physical Symptom Score From Baseline (2-7 Days Post Randomization) Until 4 Weeks Post Randomization

  4 weeks post randomization

Other Outcomes (6)

• Viral Factors in HSIL Progression to Cancer

  Up to 5 years after randomization

• Host Factors in HSIL Progression to Cancer

  Up to 5 years after randomization

• Host and Viral Biomarkers of Progression From HSIL to Cancer

  Up to 5 years after randomization

Study Arms (2)

Arm I (treatment)

EXPERIMENTAL

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.

Drug: imiquimod; Drug: fluorouracil; Device: infrared photocoagulation therapy; Device: thermal ablation therapy; Device: laser therapy; Other: clinical observation; Other: laboratory biomarker analysis

Arm II (active monitoring) (closed since SEP2021)

ACTIVE COMPARATOR

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.

Other: clinical observation; Other: laboratory biomarker analysis

Interventions

imiquimod DRUG

Applied topically

Also known as: Aldara, IMQ, R 837

Arm I (treatment)

fluorouracil DRUG

Applied topically

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU, Efudex

Arm I (treatment)

infrared photocoagulation therapy DEVICE

Undergo infrared coagulation

Also known as: infrared coagulation, IRC

Arm I (treatment)

thermal ablation therapy DEVICE

Undergo hyfrecation/electrocautery therapy

Arm I (treatment)

laser therapy DEVICE

Undergo laser therapy

Also known as: therapy, laser

Arm I (treatment)

clinical observation OTHER

Undergo active monitoring (High Resolution Anoscopy \[HRA\]) with biopsies

Also known as: observation

Arm I (treatment); Arm II (active monitoring) (closed since SEP2021)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (treatment); Arm II (active monitoring) (closed since SEP2021)

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV positive. Documentation of HIV-1 infection by means of any one of the following: 1) Documentation of HIV diagnosis in the medical record by a licensed health care provider; 2) Documentation of receipt of ART by a licensed health care provider (receipt of at least two agents is required); 3) HIV-1 RNA detection by a licensed HIV-1 RNA assay demonstrating \>1000 RNA copies/mL; or, 4) 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.
• 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, documentation that the participant is being followed for cervical cytology (if having a cervix) and/or HPV testing per current ASCCP guidelines, and visual examination of the vulva, vagina, and cervix to rule out cancer/suspicion for cancer 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 or more), 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 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.
• 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

You may not qualify if:

• Inability to provide informed consent
• Patients who are receiving any other immunomodulatory investigational agents (replacement doses of steroids for adrenal insufficiency or treatment with prednisone ≤5 mg/day is permitted) within the 4 weeks before randomization enrollment, other than investigational antiretroviral agents for HIV, or investigational or approved agents for Hepatitis C.
• History of anal cancer, penile, vulvar, vaginal or cervical cancer, or signs of these cancers at baseline.
• Treatment or removal of HSIL less than 6 months prior to randomization.
• 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
• 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 without an ANCHOR study site during study participation

Sponsors & Collaborators

• AIDS Malignancy Consortium: lead
• National Cancer Institute (NCI): collaborator
• The Emmes Company, LLC: collaborator
• University of Arkansas: collaborator
• University of California, San Francisco: collaborator
• University of Arizona: collaborator

Study Sites (25)

UCLA CARE Clinic

Los Angeles, California, 90035, United States

Location

UCLA School of Nursing

Los Angeles, California, 90095, United States

Location

DAP Health

Palm Springs, California, 92262, United States

Location

University of California at San Francisco Anal Dysplasia Clinic

San Francisco, California, 94115, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Denver Public Health

Denver, Colorado, 80204, United States

Location

Capital Digestive Care

Washington D.C., District of Columbia, 20006, United States

Location

Dupont Circle Physicians Group

Washington D.C., District of Columbia, 20009, United States

Location

ACC Clinic, Jackson Hospital

Miami, Florida, 33136, United States

Location

University of Miami Miller School of Medicine - Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Grady Health System

Atlanta, Georgia, 30303, United States

Location

Anal Dysplasia Clinic MidWest

Chicago, Illinois, 60614, United States

Location

University Medical Center New Orleans

New Orleans, Louisiana, 70112, United States

Location

CrescentCare Health

New Orleans, Louisiana, 70119, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Fenway Health

Boston, Massachusetts, 02215, United States

Location

Rutgers University New Jersey Medical School

Newark, New Jersey, 07103, United States

Location

Cornell Clinical Trials Unit, Chelsea Center

New York, New York, 10010, United States

Location

Laser Surgery Care

New York, New York, 10011, United States

Location

Montefiore - Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

The Polyclinic

Seattle, Washington, 98104, United States

Location

University of Puerto Rico

San Juan, 00936, Puerto Rico

Location

Related Publications (4)

• Lee JY, Lensing SY, Berry-Lawhorn JM, Jay N, Darragh TM, Goldstone SE, Wilkin TJ, Stier EA, Einstein M, Pugliese JC, Palefsky JM; ANCHOR Investigators. Design of the ANal Cancer/HSIL Outcomes Research study (ANCHOR study): A randomized study to prevent anal cancer among persons living with HIV. Contemp Clin Trials. 2022 Feb;113:106679. doi: 10.1016/j.cct.2022.106679. Epub 2022 Jan 10.

  PMID: 35017115 BACKGROUND

• Palefsky JM, Lee JY, Jay N, Goldstone SE, Darragh TM, Dunlevy HA, Rosa-Cunha I, Arons A, Pugliese JC, Vena D, Sparano JA, Wilkin TJ, Bucher G, Stier EA, Tirado Gomez M, Flowers L, Barroso LF, Mitsuyasu RT, Lensing SY, Logan J, Aboulafia DM, Schouten JT, de la Ossa J, Levine R, Korman JD, Hagensee M, Atkinson TM, Einstein MH, Cracchiolo BM, Wiley D, Ellsworth GB, Brickman C, Berry-Lawhorn JM; ANCHOR Investigators Group. Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. N Engl J Med. 2022 Jun 16;386(24):2273-2282. doi: 10.1056/NEJMoa2201048.

  PMID: 35704479 RESULT

• Barroso LF, Stier EA, Hillman R, Palefsky J. Anal Cancer Screening and Prevention: Summary of Evidence Reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infection Guidelines. Clin Infect Dis. 2022 Apr 13;74(Suppl_2):S179-S192. doi: 10.1093/cid/ciac044.

  PMID: 35416975 DERIVED

• Higashi RT, Rodriguez SA, Betts AC, Tiro JA, Luque AE, Rivera R, Barnes A. Anal cancer screening among women with HIV: provider experiences and system-level challenges. AIDS Care. 2022 Feb;34(2):220-226. doi: 10.1080/09540121.2021.1883512. Epub 2021 Feb 17.

  PMID: 33594934 DERIVED

MeSH Terms

Conditions

Anus Neoplasms; Squamous Intraepithelial Lesions; HIV Infections; Papillomavirus Infections; Acquired Immunodeficiency Syndrome

Interventions

Imiquimod; Fluorouracil; Light Coagulation; Laser Therapy; Watchful Waiting; Observation

Condition Hierarchy (Ancestors)

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases; Morphological and Microscopic Findings; Pathological Conditions, Signs and Symptoms; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; DNA Virus Infections; Tumor Virus Infections; Disease Attributes; Pathologic Processes; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Hemostatic Techniques; Therapeutics; Hemostasis, Surgical; Surgical Procedures, Operative; Ophthalmologic Surgical Procedures; Ablation Techniques; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Methods; Investigative Techniques

Results Point of Contact

• Title: Dr. Joel Palefsky
• Organization: University of California, San Francisco

joel.palefsky@ucsf.edu

(415) 476-1574

Study Officials

• Joel Palefsky, MD

  AIDS Malignancy Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: All participants are evaluated with high resolution anoscopy and anal cytology every 6 months during study participation. Participants randomized to treatment undergo biopsy of anal HSIL at each 6-month visit, and receive topical or ablative therapies for incident anal HSIL lesions. Active monitoring participants undergo close observation, with biopsy of anal HSIL at annual visits. Participants undergo biopsy of lesions at any time cancer is suspected.

Study Record Dates

• First Submitted: May 8, 2014
• First Posted: May 12, 2014
• Study Start: September 24, 2014
• Primary Completion: August 6, 2021
• Study Completion: March 31, 2024
• Last Updated: July 26, 2024
• Results First Posted: December 2, 2022

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: IPD will only be shared with external investigators following conclusion of all participant data collection and the acceptance of a manuscript(s) that addresses all trial objectives, via release of the data to a public data repository, anticipated to occur on or after August 2025. Data will be available according to the archival terms of the AMC Data Commons.
• Access Criteria: Qualified researchers with plans approved by the AMC Executive Committee who have entered into a Data Use Agreement (DUA) with the AMC will be granted data access. Research plans may include, but are not limited to, research on HIV/AIDS, anal HSIL screening and/or treatment, HPV-associated malignancies, anal cancer, and associated conditions.

Locations

US (24); PR (1)