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

NCT ID: NCT02135419

Last Updated: 2024-07-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

4446 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-09-24

Study Completion Date

2024-03-31

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVES: The primary objective of this study has been completed for efficacy.

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

II. To assess the responsiveness (sensitivity to change) and clinical significance of the ANCHOR Health-Related Symptom Index (A-HRSI) subscales by comparing change scores within groups of participants as defined by participant responses to the participant global impression of change (PGIC) item. (completed FEB2020)

TERTIARY OBJECTIVES:

Collect clinical specimens and data to create a bank of well-annotated specimens that will enable correlative science:

I. Identification of viral factors in HSIL progression to cancer; II. Identification of host factors in HSIL progression to cancer; III. Identify host and viral biomarkers of progression from HSIL to cancer; IV. Identify medical history and behavioral risk factors for HSIL progression to cancer.

QUALITY OF LIFE OBJECTIVES (completed FEB2022) I. Primary QOL Objective: To compare arms in terms of changes in physical symptoms and impacts from T2 to T3, adjusting for T1.

ANCILLARY (COVID SUPPLEMENT) SUBSTUDY OBJECTIVES:

I. Determine the prevalence of SARS-CoV-2 detection in anal and oropharyngeal swabs among people living with HIV (PLWH) being screened for and enrolled in the ANCHOR study.

II. Determine the relationship between prevalent anal SARS-CoV-2 positivity, anal HPV infection, and anal high-grade squamous intraepithelial lesions (HSIL).

III. Determine the 6-month incidence of SARS-CoV-2 detection in anal and oropharyngeal swabs among participants in the active monitoring arm being assessed for the first time for treatment and individuals already enrolled in the COVID substudy under protocol version 15.0.

IV. Determine the relationship between prevalent or incident SARS-CoV-2 detection and regression of anal HPV infection or HSIL among active monitoring arm participants already enrolled in the COVID substudy under protocol version 15.0, and those who continue the protocol and who choose not to be treated at visit 101.

OUTLINE: The randomized strategy to study the efficacy of HSIL treatment to reduce the risk of progression to anal cancer, as compared to active monitoring, was discontinued for all participants.

Patients are randomized to 1 of 2 treatment arms. (accrual closed SEP2021)

ARM I: Patients are directed to receive either topical or ablative treatment at the discretion of the clinician. Patients receiving topical treatment apply topical imiquimod intra-anally, peri-anally or both thrice weekly for up to 16 weeks, or topical 5-fluorouracil twice daily for 5 days every 2 weeks for up to 16 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 HRA examinations and anal cytology every 6 months. Every 12 months, patients undergo biopsies of visible lesions.

Participants on both arms are to be followed for up to 5 years after randomization of the last participant.

Post-randomization phase: Individuals in the treatment arm may continue treatment, and participants in the active monitoring arm are offered treatment. If upon assessment participants continue to have HSIL but do not intend to get treatment, they will be monitored for the potential for disease progression to anal cancer.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

imiquimod

Intervention Type DRUG

Applied topically

fluorouracil

Intervention Type DRUG

Applied topically

infrared photocoagulation therapy

Intervention Type DEVICE

Undergo infrared coagulation

thermal ablation therapy

Intervention Type DEVICE

Undergo hyfrecation/electrocautery therapy

laser therapy

Intervention Type DEVICE

Undergo laser therapy

clinical observation

Intervention Type OTHER

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

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Arm II (active monitoring) (closed since SEP2021)

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.

Group Type ACTIVE_COMPARATOR

clinical observation

Intervention Type OTHER

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

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

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imiquimod

Applied topically

Intervention Type DRUG

fluorouracil

Applied topically

Intervention Type DRUG

infrared photocoagulation therapy

Undergo infrared coagulation

Intervention Type DEVICE

thermal ablation therapy

Undergo hyfrecation/electrocautery therapy

Intervention Type DEVICE

laser therapy

Undergo laser therapy

Intervention Type DEVICE

clinical observation

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

Intervention Type OTHER

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

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Aldara IMQ R 837 5-fluorouracil 5-Fluracil 5-FU Efudex infrared coagulation IRC therapy, laser observation

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

The Emmes Company, LLC

INDUSTRY

Sponsor Role collaborator

University of Arkansas

OTHER

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role collaborator

University of Arizona

OTHER

Sponsor Role collaborator

AIDS Malignancy Consortium

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Joel Palefsky, MD

Role: PRINCIPAL_INVESTIGATOR

AIDS Malignancy Consortium

Locations

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UCLA CARE Clinic

Los Angeles, California, United States

Site Status

UCLA School of Nursing

Los Angeles, California, United States

Site Status

DAP Health

Palm Springs, California, United States

Site Status

University of California at San Francisco Anal Dysplasia Clinic

San Francisco, California, United States

Site Status

University of Colorado Hospital

Aurora, Colorado, United States

Site Status

Denver Public Health

Denver, Colorado, United States

Site Status

Capital Digestive Care

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

Site Status

Dupont Circle Physicians Group

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

Site Status

ACC Clinic, Jackson Hospital

Miami, Florida, United States

Site Status

University of Miami Miller School of Medicine - Sylvester Cancer Center

Miami, Florida, United States

Site Status

Grady Health System

Atlanta, Georgia, United States

Site Status

Anal Dysplasia Clinic MidWest

Chicago, Illinois, United States

Site Status

University Medical Center New Orleans

New Orleans, Louisiana, United States

Site Status

CrescentCare Health

New Orleans, Louisiana, United States

Site Status

Boston Medical Center

Boston, Massachusetts, United States

Site Status

Fenway Health

Boston, Massachusetts, United States

Site Status

Rutgers University New Jersey Medical School

Newark, New Jersey, United States

Site Status

Cornell Clinical Trials Unit, Chelsea Center

New York, New York, United States

Site Status

Laser Surgery Care

New York, New York, United States

Site Status

Montefiore - Albert Einstein College of Medicine

The Bronx, New York, United States

Site Status

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Site Status

Virginia Mason Medical Center

Seattle, Washington, United States

Site Status

Harborview Medical Center

Seattle, Washington, United States

Site Status

The Polyclinic

Seattle, Washington, United States

Site Status

University of Puerto Rico

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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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.

Reference Type BACKGROUND
PMID: 35017115 (View on PubMed)

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.

Reference Type RESULT
PMID: 35704479 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35416975 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33594934 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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NCI-2014-00636

Identifier Type: REGISTRY

Identifier Source: secondary_id

AMC-A01

Identifier Type: OTHER

Identifier Source: secondary_id

AMC-A01

Identifier Type: OTHER

Identifier Source: secondary_id

U01CA121947

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UM1CA121947

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ANCHOR

Identifier Type: OTHER

Identifier Source: secondary_id

AMC-A01

Identifier Type: -

Identifier Source: org_study_id

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