Trial Outcomes & Findings for Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Lesions (NCT NCT02135419)
NCT ID: NCT02135419
Last Updated: 2024-07-26
Results Overview
Anal cancer incidence is calculated as the number of anal cancer cases detected per 100,000 person years
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
4446 participants
Primary outcome timeframe
Time from randomization to diagnosis of anal cancer, assessed up to 5 years post randomization
Results posted on
2024-07-26
Participant Flow
Participant milestones
| Measure |
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.
imiquimod: Applied topically
fluorouracil: Applied topically
infrared photocoagulation therapy: Undergo infrared coagulation
thermal ablation therapy: Undergo hyfrecation/electrocautery therapy
laser therapy: Undergo laser therapy
clinical observation: Undergo active monitoring (High Resolution Anoscopy \[HRA\]) with biopsies
laboratory biomarker analysis: 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.
clinical observation: Undergo active monitoring (High Resolution Anoscopy \[HRA\]) with biopsies
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Overall Study
STARTED
|
2227
|
2219
|
|
Overall Study
COMPLETED
|
2071
|
2080
|
|
Overall Study
NOT COMPLETED
|
156
|
139
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Lesions
Baseline characteristics by cohort
| Measure |
Arm I (Treatment)
n=2227 Participants
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.
imiquimod: Applied topically
fluorouracil: Applied topically
infrared photocoagulation therapy: Undergo infrared coagulation
thermal ablation therapy: Undergo hyfrecation/electrocautery therapy
laser therapy: Undergo laser therapy
clinical observation: Undergo active monitoring (High Resolution Anoscopy \[HRA\]) with biopsies
laboratory biomarker analysis: Correlative studies
|
Arm II (Active Monitoring) (Closed Since SEP2021)
n=2219 Participants
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.
clinical observation: Undergo active monitoring (High Resolution Anoscopy \[HRA\]) with biopsies
laboratory biomarker analysis: Correlative studies
|
Total
n=4446 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.9 years
STANDARD_DEVIATION 8.9 • n=5 Participants
|
50.9 years
STANDARD_DEVIATION 9.0 • n=7 Participants
|
50.9 years
STANDARD_DEVIATION 8.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
342 Participants
n=5 Participants
|
354 Participants
n=7 Participants
|
696 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1885 Participants
n=5 Participants
|
1865 Participants
n=7 Participants
|
3750 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
594 Participants
n=5 Participants
|
502 Participants
n=7 Participants
|
1096 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
1582 Participants
n=5 Participants
|
1665 Participants
n=7 Participants
|
3247 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
51 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
103 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
11 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
27 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
4 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
935 Participants
n=5 Participants
|
939 Participants
n=7 Participants
|
1874 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
1017 Participants
n=5 Participants
|
1016 Participants
n=7 Participants
|
2033 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
89 Participants
n=5 Participants
|
98 Participants
n=7 Participants
|
187 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
144 Participants
n=5 Participants
|
118 Participants
n=7 Participants
|
262 Participants
n=5 Participants
|
|
Region of Enrollment
Puerto Rico
|
110 participants
n=5 Participants
|
110 participants
n=7 Participants
|
220 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
2117 participants
n=5 Participants
|
2109 participants
n=7 Participants
|
4226 participants
n=5 Participants
|
|
CD4 count
|
602 cells/mm^3
n=5 Participants
|
607 cells/mm^3
n=7 Participants
|
604 cells/mm^3
n=5 Participants
|
PRIMARY outcome
Timeframe: Time from randomization to diagnosis of anal cancer, assessed up to 5 years post randomizationPopulation: Participants who were randomized and received the assigned intervention
Anal cancer incidence is calculated as the number of anal cancer cases detected per 100,000 person years
Outcome measures
| Measure |
Arm I (Treatment)
n=2227 Participants
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.
imiquimod: Applied topically
fluorouracil: Applied topically
infrared photocoagulation therapy: Undergo infrared coagulation
thermal ablation therapy: Undergo hyfrecation/electrocautery therapy
laser therapy: Undergo laser therapy
clinical observation: Undergo active monitoring (High Resolution Anoscopy \[HRA\]) with biopsies
laboratory biomarker analysis: Correlative studies
|
Arm II (Active Monitoring) (Closed Since SEP2021)
n=2219 Participants
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.
clinical observation: Undergo active monitoring (High Resolution Anoscopy \[HRA\]) with biopsies
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Anal Cancer Incidence
|
173 cases per 100,000 person years
Interval 90.0 to 332.0
|
402 cases per 100,000 person years
Interval 262.0 to 616.0
|
SECONDARY outcome
Timeframe: Up to 5 years after randomizationPopulation: Participants who received assigned intervention
Participants who had at least one adverse event (serious or non-serious)
Outcome measures
| Measure |
Arm I (Treatment)
n=2227 Participants
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.
imiquimod: Applied topically
fluorouracil: Applied topically
infrared photocoagulation therapy: Undergo infrared coagulation
thermal ablation therapy: Undergo hyfrecation/electrocautery therapy
laser therapy: Undergo laser therapy
clinical observation: Undergo active monitoring (High Resolution Anoscopy \[HRA\]) with biopsies
laboratory biomarker analysis: Correlative studies
|
Arm II (Active Monitoring) (Closed Since SEP2021)
n=2219 Participants
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.
clinical observation: Undergo active monitoring (High Resolution Anoscopy \[HRA\]) with biopsies
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Incidence of Adverse Events for Each Treatment
|
416 Participants
|
429 Participants
|
SECONDARY outcome
Timeframe: 4 weeks post randomizationPopulation: Participants who were randomized on the ANCHOR study and for whom physical symptom scores were obtained at baseline and 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.
Outcome measures
| Measure |
Arm I (Treatment)
n=46 Participants
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.
imiquimod: Applied topically
fluorouracil: Applied topically
infrared photocoagulation therapy: Undergo infrared coagulation
thermal ablation therapy: Undergo hyfrecation/electrocautery therapy
laser therapy: Undergo laser therapy
clinical observation: Undergo active monitoring (High Resolution Anoscopy \[HRA\]) with biopsies
laboratory biomarker analysis: Correlative studies
|
Arm II (Active Monitoring) (Closed Since SEP2021)
n=38 Participants
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.
clinical observation: Undergo active monitoring (High Resolution Anoscopy \[HRA\]) with biopsies
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Change in Physical Symptom Score From Baseline (2-7 Days Post Randomization) Until 4 Weeks Post Randomization
|
-2.22 score on a scale
Standard Deviation 4.69
|
-0.08 score on a scale
Standard Deviation 3.31
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 years after randomizationDescriptive 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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 years after randomizationLinear 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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 years after randomizationBiomarkers that are correlated with progression from anal HSIL to anal cancer
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 years after randomizationFor 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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 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).
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 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.
Outcome measures
Outcome data not reported
Adverse Events
Arm I (Treatment)
Serious events: 370 serious events
Other events: 82 other events
Deaths: 55 deaths
Arm II (Active Monitoring) (Closed Since SEP2021)
Serious events: 375 serious events
Other events: 60 other events
Deaths: 48 deaths
Serious adverse events
| Measure |
Arm I (Treatment)
n=2227 participants at risk
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.
imiquimod: Applied topically
fluorouracil: Applied topically
infrared photocoagulation therapy: Undergo infrared coagulation
thermal ablation therapy: Undergo hyfrecation/electrocautery therapy
laser therapy: Undergo laser therapy
clinical observation: Undergo active monitoring (High Resolution Anoscopy \[HRA\]) with biopsies
laboratory biomarker analysis: Correlative studies
|
Arm II (Active Monitoring) (Closed Since SEP2021)
n=2219 participants at risk
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.
clinical observation: Undergo active monitoring (High Resolution Anoscopy \[HRA\]) with biopsies
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Infections and infestations
Lung Infection
|
1.4%
31/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
1.2%
27/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Infections and Infestations, other
|
1.2%
27/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
1.4%
31/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms
|
2.5%
56/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
2.5%
56/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Cardiac disorders
Myocardial Infarction
|
0.67%
15/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.50%
11/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Cardiac disorders
Chest pain - cardiac
|
0.40%
9/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.18%
4/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Cardiac disorders
Heart Failure
|
0.22%
5/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.45%
10/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Sepsis
|
0.81%
18/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.45%
10/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Skin Infection
|
0.90%
20/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.77%
17/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Urinary tract infection
|
0.49%
11/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.18%
4/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Injury, poisoning and procedural complications
Fracture
|
0.58%
13/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.23%
5/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
|
0.18%
4/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.77%
17/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Psychiatric disorders
Depression
|
0.31%
7/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.27%
6/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Psychiatric disorders
Suicide attempt
|
0.18%
4/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.23%
5/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Renal and urinary disorders
Acute kidney injury
|
0.18%
4/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.41%
9/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Renal and urinary disorders
Chronic kidney disease
|
0.22%
5/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.27%
6/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Blood and lymphatic system disorders
Anemia
|
0.18%
4/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.14%
3/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Cardiac disorders
Cardiac arrest
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.32%
7/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Cardiac disorders
Cardiac disorders - other
|
0.27%
6/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.14%
3/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Abdominal pain
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.14%
3/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Colitis
|
0.13%
3/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.27%
6/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
enterocolitis
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.18%
4/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.13%
3/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.32%
7/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
General disorders
Death NOS
|
0.58%
13/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.45%
10/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Hepatobiliary disorders
Cholecystitis
|
0.22%
5/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.27%
6/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Anorectal infecton
|
0.18%
4/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Appendicitis
|
0.18%
4/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Appendicitis perforated
|
0.13%
3/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Bone infection
|
0.27%
6/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.27%
6/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Bronchial infection
|
0.13%
3/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Enterocolitis infection
|
0.18%
4/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.23%
5/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Soft Tissue Infection
|
0.22%
5/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.18%
4/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Metabolism and nutrition disorders
Dehydration
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.18%
4/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.22%
5/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.18%
4/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Nervous system disorders
Stroke
|
0.49%
11/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.63%
14/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Nervous system disorders
Seizure
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.23%
5/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Psychiatric disorders
Psychiatric disorders, other
|
0.18%
4/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Psychiatric disorders
Suicidal ideation
|
0.18%
4/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.23%
5/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.18%
4/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Cardiac disorders
Aortic valve disease
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.14%
3/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders, other
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Cardiac disorders
Mitral valve disease
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Cardiac disorders
Ventricular arrythmia
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Congenital, familial and genetic disorders
Congenital, familial and genetic disorders, other
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Ear and labyrinth disorders
Vertigo
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Anal hemorrhage
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Colonic Fistula
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Colonic hemorrhage
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Colonic obstruction
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Colonic perforation
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Diarrhea
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.14%
3/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Gastric hemorrhage
|
0.13%
3/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Gastritis
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Gastrointestinal disorder, other
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.14%
3/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Pancreatitis
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Abdominal infection
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Device related infection
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Joint infection
|
0.13%
3/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Meningitis
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Pelvic infection
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Shingles
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.14%
3/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Thrush
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Upper Gastrointestinal hemorrhage
|
0.18%
4/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Vomiting
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
General disorders
Fever
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
General disorders
Flu-like symptoms
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
General disorders
Non-cardiac chest pain
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
General disorders
Pain
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Hepatobiliary disorders
Gallbladder obstruction
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Hepatobiliary disorders
Hepatitis failure
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Immune system disorders
Allergic reaction
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Upper respiratory infection
|
0.31%
7/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Viremia
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Wound infection
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
General disorders
Sudden death, NOS
|
0.27%
6/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.14%
3/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
Other adverse events
| Measure |
Arm I (Treatment)
n=2227 participants at risk
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.
imiquimod: Applied topically
fluorouracil: Applied topically
infrared photocoagulation therapy: Undergo infrared coagulation
thermal ablation therapy: Undergo hyfrecation/electrocautery therapy
laser therapy: Undergo laser therapy
clinical observation: Undergo active monitoring (High Resolution Anoscopy \[HRA\]) with biopsies
laboratory biomarker analysis: Correlative studies
|
Arm II (Active Monitoring) (Closed Since SEP2021)
n=2219 participants at risk
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.
clinical observation: Undergo active monitoring (High Resolution Anoscopy \[HRA\]) with biopsies
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Infections and infestations
Infections and Infestations, other
|
1.8%
40/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
1.6%
36/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Cardiac disorders
Cardiac Disorders, Other
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Cardiac disorders
Chest pain - cardiac
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Eye disorders
Cataract
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Anal fissure
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Anal hemorrhage
|
0.18%
4/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Anal pain
|
0.85%
19/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.14%
3/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Anal ulcer
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Colitis
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Constipation
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Diarrhea
|
0.13%
3/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Gastrointestinal disorder, other
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Hemorrhoids
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Anorectal infection
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.09%
2/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms, other
|
0.18%
4/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Surgical and medical procedures
Surgical and Medical procedures, other
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Vascular disorders
Hypertension
|
0.09%
2/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.18%
4/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Gastrointestinal disorders
Anal fistula
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Lung infection
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Sinusitis
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Skin infection
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Infections and infestations
Upper respiratory infection
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications, other
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Injury, poisoning and procedural complications
Wound complication
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Nervous system disorders
Cognitive Disturbance
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Nervous system disorders
Transient ischemic attack
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy, puerperium and perinatal conditions, other
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Renal and urinary disorders
Urinary retention
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.05%
1/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.04%
1/2227 • Adverse events were collected from randomization until up to 5 years after randomization
|
0.00%
0/2219 • Adverse events were collected from randomization until up to 5 years after randomization
|
Additional Information
Dr. Joel Palefsky
University of California, San Francisco
Phone: (415) 476-1574
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place