Topical or Ablative Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Squamous Intraepithelial Lesions (ANCHOR)
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|ClinicalTrials.gov Identifier: NCT02135419|
Recruitment Status : Recruiting
First Posted : May 12, 2014
Last Update Posted : July 27, 2020
|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|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||5058 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||ANCHOR Study: Anal Cancer/HSIL Outcomes Research Study|
|Actual Study Start Date :||September 24, 2014|
|Estimated Primary Completion Date :||June 30, 2026|
|Estimated Study Completion Date :||June 30, 2026|
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.
Device: infrared photocoagulation therapy
Undergo infrared coagulation
Device: thermal ablation therapy
Undergo hyfrecation/electrocautery therapy
Device: laser therapy
Undergo laser therapy
Other Name: therapy, laser
Other: laboratory biomarker analysis
Active Comparator: Arm II (active monitoring)
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
Other Name: observation
Other: laboratory biomarker analysis
- Time to anal cancer [ Time Frame: Time from randomization to diagnosis of anal cancer, assessed up to 5 years ]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.
- Incidence of adverse events for each treatment [ Time Frame: Up to 5 years ]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 ]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.
- Viral factors in HSIL progression to cancer [ Time Frame: Up to 5 years ]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 ]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 ]
- Behavioral risk factors for HSIL progression to cancer [ Time Frame: Up to 5 years ]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.
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
|Contact: Abigail Arons, MPHemail@example.com|
|Contact: Jason Johnson Peretz, M.Philfirstname.lastname@example.org|
|Principal Investigator:||Joel Palefsky, MD||AIDS Malignancy Consortium|