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Trial record 1 of 1 for:    Anal Cancer HSIL Outcomes Research anchor | HPV | United States
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Topical or Ablative Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Squamous Intraepithelial Lesions (ANCHOR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02135419
Recruitment Status : Active, not recruiting
First Posted : May 12, 2014
Last Update Posted : June 21, 2022
Sponsor:
Collaborators:
National Cancer Institute (NCI)
The Emmes Company, LLC
University of Arkansas
University of California, San Francisco
University of Arizona
Information provided by (Responsible Party):
AIDS Malignancy Consortium

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.


Condition or disease Intervention/treatment Phase
Anal Cancer High-grade Squamous Intraepithelial Lesion HIV Infection Human Papilloma Virus Infection Drug: imiquimod Drug: fluorouracil Device: infrared photocoagulation therapy Device: thermal ablation therapy Device: laser therapy Other: clinical observation Other: laboratory biomarker analysis Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4459 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Prevention
Official Title: ANCHOR Study: Anal Cancer/HSIL Outcomes Research Study
Actual Study Start Date : September 24, 2014
Actual Primary Completion Date : August 6, 2021
Estimated Study Completion Date : September 30, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 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
Applied topically
Other Names:
  • Aldara
  • IMQ
  • R 837

Drug: fluorouracil
Applied topically
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
  • Efudex

Device: infrared photocoagulation therapy
Undergo infrared coagulation
Other Names:
  • infrared coagulation
  • IRC

Device: thermal ablation therapy
Undergo hyfrecation/electrocautery therapy

Device: laser therapy
Undergo laser therapy
Other Name: therapy, laser

Other: clinical observation
Undergo active monitoring (High Resolution Anoscopy [HRA]) with biopsies
Other Name: observation

Other: laboratory biomarker analysis
Correlative studies

Active Comparator: 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.
Other: clinical observation
Undergo active monitoring (High Resolution Anoscopy [HRA]) with biopsies
Other Name: observation

Other: laboratory biomarker analysis
Correlative studies




Primary Outcome Measures :
  1. Time to anal cancer [ Time Frame: Time from randomization to diagnosis of anal cancer, assessed up to 5 years after randomization of the last participant ]
    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 :
  1. Incidence of adverse events for each treatment [ Time Frame: Up to 5 years after randomization of the last participant ]
    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.

  2. Scale responsiveness of A-HRSI symptom index (completed February 2020) [ Time Frame: Baseline, 2-10 weeks, and up to 16 weeks after randomization ]
    Change between Patient Global Index of Change (PGIC) response item as analyzed by corresponding A-HRSI change in score, evaluated using one-way ANOVA across 3 groups: across 3 groups (worse, no change, and better).


Other Outcome Measures:
  1. Viral factors in HSIL progression to cancer [ Time Frame: Up to 5 years after randomization of the last participant ]
    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.

  2. Host factors in HSIL progression to cancer [ Time Frame: Up to 5 years after randomization of the last participant ]
    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.

  3. Host and viral biomarkers of progression from HSIL to cancer [ Time Frame: Up to 5 years after randomization of the last participant ]
  4. Behavioral risk factors for HSIL progression to cancer [ Time Frame: Up to 5 years after randomization of the last participant ]
    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.

  5. ANCHOR Study Health-Related Symptom Index (A-HRSI) scale responsiveness (sensitivity to change) [ Time Frame: A-HRSI and self-reported Patient Global Impression of Change (PGIC) scale and ECOG Performance Status (ECOG PS) item were administered at time of enrollment (T1) up until time of trial randomization (T2), and 71-112 days post-randomization (T3). ]
    Participants at follow-up timepoints were categorized into two sets of three groups based on PGIC and ECOG PS responses ("worse," "no change," "better"), with the primary responsiveness analysis using these three groups in a one-way analysis of variance (ANOVA).

  6. Quality of life assessment measured by the A-HRSI (validated tool) [ Time Frame: A-HRSI completion occurred at 3 time points: Pre-randomization (T1), within 2-7 days (T2) and at 4 weeks of treatment/randomization (T3). ]
    A-HRSI physical symptoms and physical impacts subscale change scores (T3 minus T2) using an analysis of covariance adjusting for the covariate baseline (T1) subscale to test for differences between arms at a one-sided 0.025 significance level with approximately 90% power.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   35 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02135419


Locations
Show Show 25 study locations
Sponsors and Collaborators
AIDS Malignancy Consortium
National Cancer Institute (NCI)
The Emmes Company, LLC
University of Arkansas
University of California, San Francisco
University of Arizona
Investigators
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Principal Investigator: Joel Palefsky, MD AIDS Malignancy Consortium
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AIDS Malignancy Consortium
ClinicalTrials.gov Identifier: NCT02135419    
Other Study ID Numbers: AMC-A01
NCI-2014-00636 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
AMC-A01 ( Other Identifier: AIDS Malignancy Consortium )
AMC-A01 ( Other Identifier: CTEP )
U01CA121947 ( U.S. NIH Grant/Contract )
UM1CA121947 ( U.S. NIH Grant/Contract )
ANCHOR ( Other Identifier: AIDS Malignancy Consortium )
First Posted: May 12, 2014    Key Record Dates
Last Update Posted: June 21, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AIDS Malignancy Consortium:
anal cancer
high-grade squamous intraepithelial lesion
anal HSIL
HIV
HIV/AIDS
human papillomavirus
HPV
Additional relevant MeSH terms:
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Papillomavirus Infections
Anus Neoplasms
Neoplasms, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Anus Diseases
Tumor Virus Infections
Infections
Communicable Diseases
Papilloma
Squamous Intraepithelial Lesions of the Cervix
Carcinoma, Squamous Cell
Carcinoma in Situ
Disease Attributes
Pathologic Processes
Virus Diseases
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Uterine Cervical Dysplasia
Precancerous Conditions
Uterine Cervical Diseases