Anal CancerPhase 3ANCHORNCT02135419
Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Lesions
A Phase 3 study testing imiquimod, fluorouracil and infrared photocoagulation therapy in people with Anal Cancer and High-grade Squamous Intraepithelial Lesion, run by AIDS Malignancy Consortium at 25 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 35 years and older
- Conditions the study is for
- Anal Cancer, High-grade Squamous Intraepithelial Lesion, HIV Infection
- What is being tested?
- imiquimod, fluorouracil and infrared photocoagulation therapy
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4,446 participants
- Where
- 25 sitesin 2 countries
- Study dates
- 24 Sep 2014to 31 Mar 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
25 sites in 2 countries.
25 sites in 2 countries
United States24 sites
Grady Health System
Atlanta, Georgia, 30303
University of Colorado Hospital
Aurora, Colorado, 80045
Boston Medical Center
Boston, Massachusetts, 02118
Fenway Health
Boston, Massachusetts, 02215
Anal Dysplasia Clinic MidWest
Chicago, Illinois, 60614
Denver Public Health
Denver, Colorado, 80204
UCLA CARE Clinic
Los Angeles, California, 90035
UCLA School of Nursing
Los Angeles, California, 90095
ACC Clinic, Jackson Hospital
Miami, Florida, 33136
University of Miami Miller School of Medicine - Sylvester Cancer Center
Miami, Florida, 33136
University Medical Center New Orleans
New Orleans, Louisiana, 70112
CrescentCare Health
New Orleans, Louisiana, 70119
Cornell Clinical Trials Unit, Chelsea Center
New York, New York, 10010
Laser Surgery Care
New York, New York, 10011
Rutgers University New Jersey Medical School
Newark, New Jersey, 07103
DAP Health
Palm Springs, California, 92262
University of California at San Francisco Anal Dysplasia Clinic
San Francisco, California, 94115
Virginia Mason Medical Center
Seattle, Washington, 98101
Harborview Medical Center
Seattle, Washington, 98104
The Polyclinic
Seattle, Washington, 98104
Montefiore - Albert Einstein College of Medicine
The Bronx, New York, 10461
Capital Digestive Care
Washington D.C., District of Columbia, 20006
Dupont Circle Physicians Group
Washington D.C., District of Columbia, 20009
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157
About this study
Official title: ANCHOR Study: Anal Cancer/HSIL Outcomes Research Study
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.
Read the detailed description
PRIMARY OBJECTIVES: The primary objective of this study has been completed for efficacy.
- 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:
- 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:
- 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:
- 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
- Anal Cancer, High-grade Squamous Intraepithelial Lesion, HIV Infection, Human Papilloma Virus Infection
- Being tested
- imiquimod, fluorouracil, infrared photocoagulation therapy, thermal ablation therapy, laser therapy
- Keywords
- anal cancer, high-grade squamous intraepithelial lesion, anal HSIL, HIV, HIV/AIDS, human papillomavirus, HPV
- Medical subject headings
- Anus Neoplasms, Squamous Intraepithelial Lesions, HIV Infections, Papillomavirus Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
imiquimodDrug
Also called Aldara, IMQ, R 837
Applied topically
fluorouracilDrug
Also called 5-fluorouracil, 5-Fluracil, 5-FU, Efudex
Applied topically
infrared photocoagulation therapyDevice
Also called infrared coagulation, IRC
Undergo infrared coagulation
thermal ablation therapyDevice
Undergo hyfrecation/electrocautery therapy
laser therapyDevice
Also called therapy, laser
Undergo laser therapy
clinical observationOther
Also called observation
Undergo active monitoring (High Resolution Anoscopy [HRA]) with biopsies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: clinical observation; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Anal Cancer Incidence
Anal cancer incidence is calculated as the number of anal cancer cases detected per 100,000 person years
Measured: 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
Participants who had at least one adverse event (serious or non-serious)
Measured: Up to 5 years after randomization
Change in Physical Symptom Score From Baseline (2-7 Days Post Randomization) Until 4 Weeks Post Randomization
The physical symptom score is made up of the sum of responses to whether or not the participant had any of the 9 physical symptoms: anal pain, pain other than anal pain, pain during bowel movements, constipation, bleeding from anus, itching in/around the anus, discharge (wetness) in anal area, burning sensations in the anal area, and urgency for bowel movements. Responses are 0- not at all, 1-a little bit, 2-somewhat, 3-quite a bit, 4-very much. Thus physical symptom score ranges from 0 to 36.
Measured: 4 weeks post randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2014 (estimated)
- Study start24 Sep 2014
- Primary completion6 Aug 2021
- Study completion31 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Anal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 4,446 participants (actual)
Sponsor and investigators
- Lead sponsor
- AIDS Malignancy Consortium
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI), The Emmes Company, LLC, University of Arkansas, University of California, San Francisco, University of Arizona
- Responsible party
- Sponsor
- Investigators
- Joel Palefsky, MD, Principal investigator, AIDS Malignancy Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02135419
- Sponsor's protocol ID
- AMC-A01
- Other IDs
- NCI-2014-00636, AMC-A01, AMC-A01, U01CA121947, UM1CA121947, ANCHOR
- Acronym
- ANCHOR
- Status last verified
- Jul 2024
- First submitted
- 8 May 2014
- Last updated
- 26 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: A CDISC-mapped, de-identified version of the study data with appropriate documentation (data dictionary, annotated static copies of electronic case report forms, clinical protocol, informed consent document) of the data elements will be made available via a public data repository: the AIDS Malignancy Consortium (AMC) Data Commons.
Publications
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.
PubMed 35017115Palefsky 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.
PubMed 35704479Barroso 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.
PubMed 35416975Higashi 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.
PubMed 33594934
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ANCHOR Study: Anal Cancer/HSIL Outcomes Research Study
- ClinicalTrials.gov ID
- NCT02135419
- Acronym / sponsor ID
- ANCHOR / AMC-A01
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4,446 participants (actual)
- Lead sponsor
- AIDS Malignancy ConsortiumResearch network
- Collaborators
- National Cancer Institute (NCI), The Emmes Company, LLC, University of Arkansas, University of California, San Francisco, University of Arizona
- Study start
- 24 Sep 2014 (actual)
- Primary completion
- 6 Aug 2021 (actual)
- Study completion
- 31 Mar 2024 (actual)
- First posted
- 12 May 2014 (estimated)
- Results
- Posted 2 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
PRIMARY OBJECTIVES: The primary objective of this study has been completed for efficacy.
- 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:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Arm I (treatment) | Experimental | Drug: imiquimod, Drug: fluorouracil, Device: infrared photocoagulation therapy, Device: thermal ablation therapy, Device: laser therapy, Other: clinical observation, Other: laboratory biomarker analysisPatients 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. |
| Arm II (active monitoring) (closed since SEP2021) | Active comparator | Other: clinical observation, Other: laboratory biomarker analysisPatients 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. |
Who may qualify
- Ages
- 35 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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%)
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| imiquimodAlso: Aldara, IMQ, R 837Applied topically | Drug | Arm I (treatment) |
| fluorouracilAlso: 5-fluorouracil, 5-Fluracil, 5-FU, EfudexApplied topically | Drug | Arm I (treatment) |
| infrared photocoagulation therapyAlso: infrared coagulation, IRCUndergo infrared coagulation | Device | Arm I (treatment) |
| thermal ablation therapyUndergo hyfrecation/electrocautery therapy | Device | Arm I (treatment) |
| laser therapyAlso: therapy, laserUndergo laser therapy | Device | Arm I (treatment) |
| clinical observationAlso: observationUndergo active monitoring (High Resolution Anoscopy [HRA]) with biopsies | Other | Arm I (treatment), Arm II (active monitoring) (closed since SEP2021) |
| laboratory biomarker analysisCorrelative studies | Other | Arm I (treatment), Arm II (active monitoring) (closed since SEP2021) |
Primary outcome
Anal Cancer Incidence
Time frame: Time from randomization to diagnosis of anal cancer, assessed up to 5 years post randomization
Anal cancer incidence is calculated as the number of anal cancer cases detected per 100,000 person years
2 secondary outcomes
Incidence of Adverse Events for Each Treatment
Time frame: Up to 5 years after randomization
Change in Physical Symptom Score From Baseline (2-7 Days Post Randomization) Until 4 Weeks Post Randomization
Time frame: 4 weeks post randomization
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 35017115Lee 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.
- Results publication: PubMed 35704479Palefsky 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.
- Derived from this study: PubMed 35416975Barroso 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.
- Derived from this study: PubMed 33594934Higashi 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.
- Individual participant dataSharing planned: Yes. A CDISC-mapped, de-identified version of the study data with appropriate documentation (data dictionary, annotated static copies of electronic case report forms, clinical protocol, informed consent document) of the data elements will be made available via a public data repository: the AIDS Malignancy Consortium (AMC) Data Commons.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joel Palefsky, MD principal investigator
AIDS Malignancy Consortium
25 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing imiquimod, fluorouracil and infrared photocoagulation therapy in people with Anal Cancer and High-grade Squamous Intraepithelial Lesion, run by AIDS Malignancy Consortium at 25 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Anal Cancer Incidence (time frame: Time from randomization to diagnosis of anal cancer, assessed up to 5 years post randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02135419, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2024.