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

This study has suspended participant recruitment.
(FDA review)
Sponsor:
Collaborators:
The EMMES Corporation
Information provided by (Responsible Party):
AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier:
NCT02135419
First received: May 8, 2014
Last updated: October 7, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Anal Cancer
High-grade Squamous Intraepithelial Lesion
HIV Infection
Human Papilloma Virus Infection
Drug: imiquimod
Drug: fluorouracil
Procedure: infrared photocoagulation therapy
Procedure: thermal ablation therapy
Procedure: laser therapy
Other: clinical observation
Other: laboratory biomarker analysis
Procedure: quality-of-life assessment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: ANCHOR Study: Anal Cancer/HSIL Outcomes Research Study

Resource links provided by NLM:


Further study details as provided by AIDS Malignancy Clinical Trials Consortium:

Primary Outcome Measures:
  • Time to anal cancer [ Time Frame: Time from randomization to diagnosis of anal cancer, assessed up to 5 years ] [ Designated as safety issue: No ]
    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:
  • Incidence of adverse events for each treatment [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    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.

  • Quality of life assessed using the Functional Assessment of Incontinence Therapy - Fecal (FAIT-F) questionnaire [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Descriptive statistics will be used for subscales and scores for each arm and each time point. General estimating equations will be used to compare the two arms with respect to subscales and scores across time points and adjustment for intra-participant variability.


Other Outcome Measures:
  • Viral factors in HSIL progression to cancer [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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.

  • Host factors in HSIL progression to cancer [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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.

  • Host and viral biomarkers of progression from HSIL to cancer [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Behavioral risk factors for HSIL progression to cancer [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 5058
Study Start Date: September 2014
Estimated Study Completion Date: June 2022
Estimated Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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.
Drug: imiquimod
Applied topically
Other Names:
  • Aldara
  • IMQ
  • R 837
Drug: fluorouracil
Applied topically
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Procedure: infrared photocoagulation therapy
Undergo infrared coagulation
Other Names:
  • infrared coagulation
  • IRC
Procedure: thermal ablation therapy
Undergo hyfrecation/electrocautery therapy
Procedure: laser therapy
Undergo laser therapy
Other Name: therapy, laser
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Active Comparator: Arm II (active monitoring)
Patients undergo active monitoring with examinations every 6 months. Every 12 months, patients undergo biopsies of visible lesions. Patients have cytology sampling performed at every visit.
Other: clinical observation
Undergo active monitoring
Other Name: observation
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   35 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infection, as documented by any federally approved, licensed HIV test performed in conjunction with screening (or enzyme-linked immunosorbent assay [ELISA], test kit, and confirmed by western blot or other approved test); alternatively, this documentation may include a record that another physician has documented that the participant has HIV infection based on prior ELISA and western blot, or other approved diagnostic tests; an approved antibody test will be used to confirm diagnosis; if the physician is treating a patient with combination antiretroviral therapy (cART) with a history of HIV positivity based on an approved antibody test then repeat antibody confirmation is not necessary
  • No history of treatment or removal of HSIL
  • No history of anal cancer or signs of anal cancer at baseline, and no history of penile, vulvar, vaginal or cervical cancer
  • 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, cervical cytology (if having a cervix) and gynecologic evaluation including vulvar examination 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), 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 in this study; men who could father a child should use at least two forms of birth control for 3 months after stopping all study 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 within the 4 weeks before randomization enrollment, other than investigational antiretroviral agents for HIV
  • History of anal cancer, penile, vulvar, vaginal or cervical cancer
  • 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
  • Prior pelvic radiation therapy that would preclude radiation therapy if anal cancer develops
  • 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 during study participation
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02135419

Locations
United States, California
University of California at San Francisco Anal Dysplasia Clinic
San Francisco, California, United States, 94115
Sponsors and Collaborators
AIDS Malignancy Clinical Trials Consortium
The EMMES Corporation
Investigators
Principal Investigator: Joel Palefsky, MD AIDS Associated Malignancies Clinical Trials Consortium
  More Information

No publications provided

Responsible Party: AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier: NCT02135419     History of Changes
Other Study ID Numbers: AMC-A01, NCI-2014-00636, AMC-A01, AMC-A01, U01CA121947
Study First Received: May 8, 2014
Last Updated: October 7, 2014
Health Authority: United States: Food and Drug Administration
United States: Federal Government
United States: Institutional Review Board
United States: Data and Safety Monitoring Board

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Anus Neoplasms
Communicable Diseases
HIV Infections
Infection
Papillomavirus Infections
Uterine Cervical Dysplasia
Virus Diseases
Anus Diseases
Colorectal Neoplasms
DNA Virus Infections
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Genital Diseases, Female
Immune System Diseases
Immunologic Deficiency Syndromes
Intestinal Diseases
Intestinal Neoplasms
Lentivirus Infections
Neoplasms
Neoplasms by Site
Precancerous Conditions
RNA Virus Infections
Rectal Diseases
Rectal Neoplasms
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral

ClinicalTrials.gov processed this record on November 19, 2014