Trial Outcomes & Findings for Imiquimod, Fluorouracil, or Observation in Treating HIV-Positive Patients With High-Grade Anal Squamous Skin Lesions (NCT NCT02059499)
NCT ID: NCT02059499
Last Updated: 2025-07-23
Results Overview
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. The percentage of participants achieving complete response in the 5-FU and observation arms will be reported and compared across sites, along with the corresponding p-value, using stratified Mantel-Haenszel-Cochran tests at a one-sided alpha level of 0.025.
COMPLETED
PHASE3
91 participants
At week 20
2025-07-23
Participant Flow
Patients were screened between December 2015 to August 2022 at one of the 11 AMC sites certified by the HPV Working Group in HRA. Participants were selected from established HSIL-positive clinic patients or referrals from physicians, such as primary care physicians, HIV specialists, dermatologists, or colorectal surgeons.
142 patients were screened using HRA, clinical examination and laboratory tests (within 90 days) to ensure they meet the eligibility criteria. 91 patients were considered eligible and assigned to one of the three study arms.
Participant milestones
| Measure |
Arm A (Imiquimod)
Patients apply imiquimod intra-anally QD for 16 weeks.
imiquimod: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm B (5-fluorouracil)
Patients apply topical 5-fluorouracil (5-FU) intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
|---|---|---|---|
|
Upto Week 20
STARTED
|
18
|
36
|
37
|
|
Upto Week 20
Population for Primary Endpoint (Week 20 Visit)
|
18
|
36
|
37
|
|
Upto Week 20
COMPLETED
|
15
|
27
|
32
|
|
Upto Week 20
NOT COMPLETED
|
3
|
9
|
5
|
|
Post-week 20
STARTED
|
15
|
27
|
13
|
|
Post-week 20
Patients Continuing Originally Assigned Treatment
|
15
|
27
|
13
|
|
Post-week 20
COMPLETED
|
12
|
20
|
4
|
|
Post-week 20
NOT COMPLETED
|
3
|
7
|
9
|
|
Cross-over Post-week 20 (Re-randomized)
STARTED
|
5
|
14
|
0
|
|
Cross-over Post-week 20 (Re-randomized)
Week 44 Visit for Initial Observation Arm Participants Who Crossed Over or Declined Crossover
|
5
|
14
|
0
|
|
Cross-over Post-week 20 (Re-randomized)
COMPLETED
|
5
|
11
|
0
|
|
Cross-over Post-week 20 (Re-randomized)
NOT COMPLETED
|
0
|
3
|
0
|
Reasons for withdrawal
| Measure |
Arm A (Imiquimod)
Patients apply imiquimod intra-anally QD for 16 weeks.
imiquimod: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm B (5-fluorouracil)
Patients apply topical 5-fluorouracil (5-FU) intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
|---|---|---|---|
|
Upto Week 20
Lost to Follow-up
|
2
|
6
|
0
|
|
Upto Week 20
Treatment completed per protocol criteria
|
0
|
2
|
0
|
|
Upto Week 20
Withdrawal by Subject
|
1
|
1
|
0
|
|
Upto Week 20
No treatment per protocol criteria
|
0
|
0
|
5
|
|
Post-week 20
Treatment not as per protocol criteria
|
3
|
4
|
9
|
|
Post-week 20
Lost to Follow-up
|
0
|
2
|
0
|
|
Post-week 20
Withdrawal by Subject
|
0
|
1
|
0
|
|
Cross-over Post-week 20 (Re-randomized)
Lost to Follow-up
|
0
|
3
|
0
|
Baseline Characteristics
Imiquimod, Fluorouracil, or Observation in Treating HIV-Positive Patients With High-Grade Anal Squamous Skin Lesions
Baseline characteristics by cohort
| Measure |
Arm A (Imiquimod)
n=18 Participants
Patients apply imiquimod intra-anally QD for 16 weeks.
imiquimod: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm B (Fluorouracil)
n=36 Participants
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
n=37 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Total
n=91 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
48.2 years
STANDARD_DEVIATION 14.3 • n=5 Participants
|
43.1 years
STANDARD_DEVIATION 12.9 • n=7 Participants
|
44.7 years
STANDARD_DEVIATION 14.0 • n=5 Participants
|
44.8 years
STANDARD_DEVIATION 13.6 • n=4 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
78 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
57 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
41 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Cytology at baseline
Normal
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Cytology at baseline
Atypical Squamous Cells of Undetermined Significance (ASCUS)
|
7 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
|
Cytology at baseline
Low-grade Squamous Intraepithelial Lesion (LSIL)
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Cytology at baseline
Atypical Squamous Cells, cannot exclude High-grade Squamous Intraepithelial Lesion (ASC-H) or HSIL
|
8 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
48 Participants
n=4 Participants
|
|
Number of octants involved as per visual appearance and biopsy performed through HRA
|
4 octant
n=5 Participants
|
4 octant
n=7 Participants
|
4 octant
n=5 Participants
|
4 octant
n=4 Participants
|
PRIMARY outcome
Timeframe: At week 20Population: ITT population
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. The percentage of participants achieving complete response in the 5-FU and observation arms will be reported and compared across sites, along with the corresponding p-value, using stratified Mantel-Haenszel-Cochran tests at a one-sided alpha level of 0.025.
Outcome measures
| Measure |
Arm C (Observation)
n=37 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm B (Fluorouracil)
n=36 Participants
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20- Fluorouracil
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20-Not Crossed Over
Participants initially randomized to Observation Arm that didn't crossover to either of the treatment arms
|
|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving Complete Response in 5-FU Arm and Observation Arm Using ITT Population
|
5 Participants
|
9 Participants
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: At week 20Population: Per protocol population
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. The percentage of participants achieving complete response in the 5-FU and observation arms will be reported, along with the corresponding p-value, using stratified Mantel-Haenszel-Cochran tests to compare results across sites at a one-sided alpha level of 0.025.
Outcome measures
| Measure |
Arm C (Observation)
n=27 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm B (Fluorouracil)
n=31 Participants
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20- Fluorouracil
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20-Not Crossed Over
Participants initially randomized to Observation Arm that didn't crossover to either of the treatment arms
|
|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving Complete Response (5-FU vs Observation ) Using Per Protocol Population
|
9 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Week 20Population: ITT population. Since the imiquimod arm was stopped early, this comparison uses only the ITT subset with participants randomized to imiquimod and 5-FU prior to closure of the imiquimod arm.
Complete response is defined as an absence of HSIL histology for all biopsies and the absence of HSIL cytology. Compare the percentage of complete response in 5-FU vs Imiquimod arms across sites using stratified CMH test at one-sided 0.05 alpha.
Outcome measures
| Measure |
Arm C (Observation)
n=18 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm B (Fluorouracil)
n=18 Participants
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20- Fluorouracil
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20-Not Crossed Over
Participants initially randomized to Observation Arm that didn't crossover to either of the treatment arms
|
|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving Complete Response in 5-FU vs. Imiquimod, Using the ITT Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
|
5 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Week 20Population: PP population restricted to those randomized to either treatment prior to the closure of the imiquimod
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. Compare the complete response by 5-FU vs Imiquimod across sites using stratified CMH test at one-sided 0.05 alpha using only the participants randomized to imiquimod and 5-FU prior to closure of the imiquimod arm.
Outcome measures
| Measure |
Arm C (Observation)
n=15 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm B (Fluorouracil)
n=14 Participants
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20- Fluorouracil
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20-Not Crossed Over
Participants initially randomized to Observation Arm that didn't crossover to either of the treatment arms
|
|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving Complete Response in 5-FU vs. Imiquimod, Using the PP Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
|
5 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Week 20Population: ITT population restricted to those randomized to either treatment prior to the closure of the imiquimod arm.
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. Compare the complete response by Observation vs Imiquimod across sites using stratified CMH test at two-sided 0.05 alpha using only the participants randomized to imiquimod and observation prior to closure of the imiquimod arm.
Outcome measures
| Measure |
Arm C (Observation)
n=18 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm B (Fluorouracil)
n=19 Participants
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20- Fluorouracil
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20-Not Crossed Over
Participants initially randomized to Observation Arm that didn't crossover to either of the treatment arms
|
|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving Complete Response in Imiquimod vs Observation Arm, Using ITT Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
|
5 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Week 20Population: PP population restricted to those randomized to either treatment prior to the closure of the imiquimod arm.
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. Compare the complete response by Observation vs Imiquimod across sites using stratified CMH test at two-sided 0.05 alpha using only the participants randomized to imiquimod and observation prior to closure of the imiquimod arm.
Outcome measures
| Measure |
Arm C (Observation)
n=15 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm B (Fluorouracil)
n=18 Participants
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20- Fluorouracil
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20-Not Crossed Over
Participants initially randomized to Observation Arm that didn't crossover to either of the treatment arms
|
|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving Complete Response in Imiquimod vs Observation Arm, Using Per Protocol Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
|
5 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: At week 20Population: Enrolled patients in each study arm
Perianal HSIL are HSIL lesions detected in peri-anal region; These lesions will be detected by visual inspection using high resolution anoscopy and biopsy. Number of participants with presence of peri-anal HSIL on histology
Outcome measures
| Measure |
Arm C (Observation)
n=18 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm B (Fluorouracil)
n=36 Participants
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
n=37 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20- Fluorouracil
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20-Not Crossed Over
Participants initially randomized to Observation Arm that didn't crossover to either of the treatment arms
|
|---|---|---|---|---|---|---|
|
Number of Participants With Peri-anal HSIL Confirmed by Histology Across All Study Arms
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: At week 20Population: ITT
Intra-anal HSIL lesions are those lesions that are detected in intra-anal region. It will be detected using visual inspection using HRA followed by positive identification of HSIL using biopsy or cytology. Presence of intra-anal HSIL lesions will be descriptively reported across the three arms
Outcome measures
| Measure |
Arm C (Observation)
n=18 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm B (Fluorouracil)
n=36 Participants
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
n=37 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20- Fluorouracil
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20-Not Crossed Over
Participants initially randomized to Observation Arm that didn't crossover to either of the treatment arms
|
|---|---|---|---|---|---|---|
|
Number of Participants With Intra-anal HSIL
|
12 Participants
|
27 Participants
|
32 Participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to week 44Population: ITT population
Adverse events are graded on a scale from 1 (mild) to 5 (death) as per CTCAE v. 5.0, with higher grades indicating greater severity. The number of participants who experienced an adverse event of grade 1 to 5 by Week 44, regardless of its relatedness to the intervention, will be reported. AEs were stratified according to those reported at or before Week 20 and after Week 20.
Outcome measures
| Measure |
Arm C (Observation)
n=18 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm B (Fluorouracil)
n=36 Participants
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
n=37 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
n=5 Participants
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20- Fluorouracil
n=14 Participants
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20-Not Crossed Over
n=13 Participants
Participants initially randomized to Observation Arm that didn't crossover to either of the treatment arms
|
|---|---|---|---|---|---|---|
|
Number of Participants Who Experienced an Adverse Event of Grade 1 to 5 by Week 44, Irrespective of Relatedness to the Intervention. AEs Were Stratified According to Those Reported at or Before Week 20 and After Week 20.
Up to week 20: Grade 1
|
0 Participants
|
2 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Who Experienced an Adverse Event of Grade 1 to 5 by Week 44, Irrespective of Relatedness to the Intervention. AEs Were Stratified According to Those Reported at or Before Week 20 and After Week 20.
Up to week 20: Grade 2
|
3 Participants
|
4 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Who Experienced an Adverse Event of Grade 1 to 5 by Week 44, Irrespective of Relatedness to the Intervention. AEs Were Stratified According to Those Reported at or Before Week 20 and After Week 20.
Up to Week 20: Grade 3
|
1 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Who Experienced an Adverse Event of Grade 1 to 5 by Week 44, Irrespective of Relatedness to the Intervention. AEs Were Stratified According to Those Reported at or Before Week 20 and After Week 20.
Up to Week 20: Grade 4
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Who Experienced an Adverse Event of Grade 1 to 5 by Week 44, Irrespective of Relatedness to the Intervention. AEs Were Stratified According to Those Reported at or Before Week 20 and After Week 20.
Up to Week 20: Grade 5
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Who Experienced an Adverse Event of Grade 1 to 5 by Week 44, Irrespective of Relatedness to the Intervention. AEs Were Stratified According to Those Reported at or Before Week 20 and After Week 20.
After week 20: Grade 1
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Who Experienced an Adverse Event of Grade 1 to 5 by Week 44, Irrespective of Relatedness to the Intervention. AEs Were Stratified According to Those Reported at or Before Week 20 and After Week 20.
After Week 20: Grade 2
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Who Experienced an Adverse Event of Grade 1 to 5 by Week 44, Irrespective of Relatedness to the Intervention. AEs Were Stratified According to Those Reported at or Before Week 20 and After Week 20.
After Week 20: Grade 3
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants Who Experienced an Adverse Event of Grade 1 to 5 by Week 44, Irrespective of Relatedness to the Intervention. AEs Were Stratified According to Those Reported at or Before Week 20 and After Week 20.
After week 20: Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Who Experienced an Adverse Event of Grade 1 to 5 by Week 44, Irrespective of Relatedness to the Intervention. AEs Were Stratified According to Those Reported at or Before Week 20 and After Week 20.
After Week 20: Grade 5
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to week 20Population: ITT
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. Partial response is defined as either 1) The regression of HSIL histology but HSIL cytology is present, or 2) Reduction in number of octants with HSIL. Percentages will be compared across sites using the stratified Mantel-Haenszel-Cochran test at the two-sided 0.05 alpha level.
Outcome measures
| Measure |
Arm C (Observation)
n=36 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm B (Fluorouracil)
n=37 Participants
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20- Fluorouracil
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20-Not Crossed Over
Participants initially randomized to Observation Arm that didn't crossover to either of the treatment arms
|
|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving Complete or Partial Response in 5-FU vs Observation Using ITT Population
|
21 Participants
|
15 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to week 20Population: ITT population restricted to those randomized to either treatment prior to the closure of the imiquimod arm.
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. Partial response is defined as 1) The regression of HSIL histology but HSIL cytology is present, or 2) Reduction in number of octants with HSIL. Percentage of patients achieving complete or partial responses with imiquimod will be compared to observation using participants randomized to imiquimod and observation prior to closure of the imiquimod arm.
Outcome measures
| Measure |
Arm C (Observation)
n=18 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm B (Fluorouracil)
n=19 Participants
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20- Fluorouracil
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20-Not Crossed Over
Participants initially randomized to Observation Arm that didn't crossover to either of the treatment arms
|
|---|---|---|---|---|---|---|
|
Percentageof Patients Achieving Complete or Partial Response in Imiquimod vs Observation Arm, Using ITT Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
|
11 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 16Population: ITT
Amount of study drug consumed by measuring the mass of study drug dispensed (weight of study drug container at baseline - weight of study drug at the end of treatment) by study arm (5FU vs imiquimod) by the time of receiving 8 cycle treatment
Outcome measures
| Measure |
Arm C (Observation)
n=18 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm B (Fluorouracil)
n=36 Participants
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20- Fluorouracil
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20-Not Crossed Over
Participants initially randomized to Observation Arm that didn't crossover to either of the treatment arms
|
|---|---|---|---|---|---|---|
|
Amount of Drug Consumed in 5-FU and Imiquimod Arm by Week 16
|
39.5 grams
Standard Deviation 7.7
|
32.6 grams
Standard Deviation 17.2
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At 44 weeksPopulation: ITT population
Complete response is defined as the Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. Partial response is defined as 1) The regression of HSIL histology but HSIL cytology is present, or 2) Reduction in number of octants with HSIL. Percentage will be compared across sites using the stratified Mantel-Haenszel-Cochran test at the two-sided 0.05 alpha level.
Outcome measures
| Measure |
Arm C (Observation)
n=36 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm B (Fluorouracil)
n=37 Participants
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20- Fluorouracil
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20-Not Crossed Over
Participants initially randomized to Observation Arm that didn't crossover to either of the treatment arms
|
|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving Complete or Partial Response in 5-FU vs Observation Using ITT Population
|
17 Participants
|
19 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to week 44Population: ITT population restricted to those randomized to either treatment prior to the closure of the imiquimod arm.
The proportion of patients achieving complete or partial responses with imiquimod will be compared to observation using participants randomized to imiquimod and observation prior to closure of the imiquimod arm. Complete response is defined as the absence of HSIL based on central pathology review, if available; otherwise, local biopsy results will be used. Partial Response is defined as: 1) The regression of HSIL histology but HSIL cytology is present, or 2) Reduction in number of octants with HSIL.
Outcome measures
| Measure |
Arm C (Observation)
n=18 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm B (Fluorouracil)
n=19 Participants
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20- Fluorouracil
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20-Not Crossed Over
Participants initially randomized to Observation Arm that didn't crossover to either of the treatment arms
|
|---|---|---|---|---|---|---|
|
Percentage of Patients Achieving Complete or Partial Response in Imiquimod vs Observation Arm, Using ITT Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
|
11 Participants
|
10 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At week 20Population: ITT
The proportion of participants with persistent HPV infection, defined as the presence of the same HPV type detected at both baseline and Week 20. The proportion of participants who acquire a new HPV infection at Week 20 that was not detected at baseline is new infection. Persistence and new infection will be assessed separately for each HPV type.
Outcome measures
| Measure |
Arm C (Observation)
n=18 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm B (Fluorouracil)
n=36 Participants
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
n=37 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20- Fluorouracil
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20-Not Crossed Over
Participants initially randomized to Observation Arm that didn't crossover to either of the treatment arms
|
|---|---|---|---|---|---|---|
|
Persistence and New Infections of HPV Type Specific Infections
Persistent : HPV 16
|
1 Participants
|
4 Participants
|
3 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
Persistent : HPV 18
|
1 Participants
|
3 Participants
|
1 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
Persistent : HPV 31
|
1 Participants
|
5 Participants
|
4 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
Persistent : HPV 33
|
0 Participants
|
1 Participants
|
2 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
Persistent : HPV 35
|
0 Participants
|
1 Participants
|
2 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
Persistent : HPV 39
|
0 Participants
|
3 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
Persistent : HPV 45
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
Persistent : HPV 51
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
Persistent : HPV 52
|
0 Participants
|
2 Participants
|
1 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
Persistent : HPV 53
|
1 Participants
|
4 Participants
|
2 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
Persistent : HPV 56
|
1 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
Persistent : HPV 58
|
2 Participants
|
1 Participants
|
3 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
Persistent : HPV 59
|
0 Participants
|
3 Participants
|
6 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
Persistent : HPV 66
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
Persistent : HPV 68
|
2 Participants
|
4 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
Persistent: any high-risk HPV infection
|
12 Participants
|
17 Participants
|
25 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
New infections : HPV 16
|
5 Participants
|
8 Participants
|
8 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
New infections : HPV 18
|
3 Participants
|
1 Participants
|
2 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
New infections : HPV 31
|
2 Participants
|
2 Participants
|
5 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
New infections : HPV 33
|
3 Participants
|
4 Participants
|
5 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
New infections : HPV 35
|
1 Participants
|
3 Participants
|
3 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
New infections : HPV 39
|
1 Participants
|
2 Participants
|
2 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
New infections : HPV 45
|
2 Participants
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
New infections : HPV 51
|
1 Participants
|
3 Participants
|
2 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
New infections : HPV 52
|
0 Participants
|
4 Participants
|
4 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
New infections : HPV 53
|
2 Participants
|
3 Participants
|
5 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
New infections : HPV 56
|
5 Participants
|
5 Participants
|
2 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
New infections : HPV 58
|
3 Participants
|
3 Participants
|
3 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
New infections : HPV 59
|
3 Participants
|
4 Participants
|
2 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
New infections : HPV 66
|
0 Participants
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
New infections : HPV 68
|
3 Participants
|
4 Participants
|
3 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
New infections: any high-risk HPV
|
11 Participants
|
21 Participants
|
26 Participants
|
—
|
—
|
—
|
|
Persistence and New Infections of HPV Type Specific Infections
Overall number of patients with hrHPV positivity at week 20
|
12 Participants
|
22 Participants
|
26 Participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: week 20Population: Per protocol
hrHPV genotypes will be detected in anal swabs specimens processed using polymerase chain reaction (PCR) and reverse line blot analysis. Comparison of mean number of hrHPV genotypes in each arm observed at baseline vs at week 20
Outcome measures
| Measure |
Arm C (Observation)
n=15 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm B (Fluorouracil)
n=27 Participants
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
n=31 Participants
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20- Fluorouracil
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20-Not Crossed Over
Participants initially randomized to Observation Arm that didn't crossover to either of the treatment arms
|
|---|---|---|---|---|---|---|
|
Comparison of the Number of hrHPV Genotypes in Each Arm Observed at Baseline vs at Week 20
Baseline
|
3.75 hrHPV genotypes
Standard Deviation 1.81
|
4.25 hrHPV genotypes
Standard Deviation 2.41
|
3.32 hrHPV genotypes
Standard Deviation 2.01
|
—
|
—
|
—
|
|
Comparison of the Number of hrHPV Genotypes in Each Arm Observed at Baseline vs at Week 20
Week 20
|
3.67 hrHPV genotypes
Standard Deviation 2.06
|
3.5 hrHPV genotypes
Standard Deviation 2.36
|
2.62 hrHPV genotypes
Standard Deviation 1.65
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 20 weeksPopulation: Per protocol
Count of HPV genotypes present at baseline but no longer detected at week 20.
Outcome measures
| Measure |
Arm C (Observation)
n=14 Unique HPV genotypes
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm B (Fluorouracil)
n=15 Unique HPV genotypes
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)
n=15 Unique HPV genotypes
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20- Fluorouracil
Participants Initially Randomized to Observation Arm Who Later Crossed Over
|
Arm C (Observation) After Week 20-Not Crossed Over
Participants initially randomized to Observation Arm that didn't crossover to either of the treatment arms
|
|---|---|---|---|---|---|---|
|
HPV Genotypes Present at Baseline But no Longer Detected at Week 20
Count and percentage of unique HPV genotypes re-detected at week 20
|
12 Unique HPV genotypes
|
15 Unique HPV genotypes
|
14 Unique HPV genotypes
|
—
|
—
|
—
|
|
HPV Genotypes Present at Baseline But no Longer Detected at Week 20
Count and percentage of unique HPV genotypes undetected at week 20
|
2 Unique HPV genotypes
|
0 Unique HPV genotypes
|
1 Unique HPV genotypes
|
—
|
—
|
—
|
Adverse Events
Arm A (Imiquimod)-Up to 44 Weeks
Arm B (Fluorouracil)- Up to 44 Weeks
Arm C (Observation)-Up to 20 Weeks
Arm C (Observation) After Week 20-Imiquimod
Arm C (Observation) After Week 20-Fluorouracil
Arm C (Observation)- After Week 20, Not Crossed Over
Serious adverse events
| Measure |
Arm A (Imiquimod)-Up to 44 Weeks
n=18 participants at risk
Patients apply imiquimod intra-anally QD for 16 weeks.
imiquimod: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm B (Fluorouracil)- Up to 44 Weeks
n=36 participants at risk
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)-Up to 20 Weeks
n=37 participants at risk
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
n=5 participants at risk
Patients initially randomized to Observation but later on agreed to crossover
|
Arm C (Observation) After Week 20-Fluorouracil
n=14 participants at risk
Patients initially randomized to Observation but later on agreed to crossover
|
Arm C (Observation)- After Week 20, Not Crossed Over
n=13 participants at risk
Patients didn't crossover to eithe fluorouracil or Imiquimod
|
|---|---|---|---|---|---|---|
|
Infections and infestations
INFECTIONS AND INFESTATIONS (BACTEREMIA)
|
0.00%
0/18 • Upto 44 Weeks
|
2.8%
1/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
0.00%
0/18 • Upto 44 Weeks
|
2.8%
1/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Vascular disorders
THROMBOEMBOLIC EVENT
|
0.00%
0/18 • Upto 44 Weeks
|
2.8%
1/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
0.00%
0/18 • Upto 44 Weeks
|
2.8%
1/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Infections and infestations
APPENDICITIS
|
0.00%
0/18 • Upto 44 Weeks
|
2.8%
1/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Infections and infestations
ENTEROCOLITIS INFECTIOUS
|
5.6%
1/18 • Upto 44 Weeks
|
2.8%
1/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Metabolism and nutrition disorders
HYPOGLYCEMIA
|
5.6%
1/18 • Upto 44 Weeks
|
0.00%
0/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Infections and infestations
LUNG INFECTION
|
5.6%
1/18 • Upto 44 Weeks
|
0.00%
0/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
Other adverse events
| Measure |
Arm A (Imiquimod)-Up to 44 Weeks
n=18 participants at risk
Patients apply imiquimod intra-anally QD for 16 weeks.
imiquimod: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm B (Fluorouracil)- Up to 44 Weeks
n=36 participants at risk
Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
fluorouracil: Given intra-anally
questionnaire administration: Ancillary studies
laboratory biomarker analysis: Correlative studies
|
Arm C (Observation)-Up to 20 Weeks
n=37 participants at risk
Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B.
|
Arm C (Observation) After Week 20-Imiquimod
n=5 participants at risk
Patients initially randomized to Observation but later on agreed to crossover
|
Arm C (Observation) After Week 20-Fluorouracil
n=14 participants at risk
Patients initially randomized to Observation but later on agreed to crossover
|
Arm C (Observation)- After Week 20, Not Crossed Over
n=13 participants at risk
Patients didn't crossover to eithe fluorouracil or Imiquimod
|
|---|---|---|---|---|---|---|
|
Metabolism and nutrition disorders
ANOREXIA
|
5.6%
1/18 • Upto 44 Weeks
|
0.00%
0/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Metabolism and nutrition disorders
HYPOGLYCEMIA
|
5.6%
1/18 • Upto 44 Weeks
|
0.00%
0/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Gastrointestinal disorders
GASTROINTESTINAL DISORDERS (Anal spasms)
|
0.00%
0/18 • Upto 44 Weeks
|
0.00%
0/36 • Upto 44 Weeks
|
2.7%
1/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER - (pain)
|
0.00%
0/18 • Upto 44 Weeks
|
0.00%
0/36 • Upto 44 Weeks
|
2.7%
1/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Nervous system disorders
HEADACHE
|
0.00%
0/18 • Upto 44 Weeks
|
0.00%
0/36 • Upto 44 Weeks
|
2.7%
1/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Surgical and medical procedures
SURGICAL AND MEDICAL PROCEDURES - (tooth filling)
|
0.00%
0/18 • Upto 44 Weeks
|
0.00%
0/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
7.1%
1/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Blood and lymphatic system disorders
LYMPH NODE PAIN
|
0.00%
0/18 • Upto 44 Weeks
|
2.8%
1/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Gastrointestinal disorders
ANAL FISSURE
|
0.00%
0/18 • Upto 44 Weeks
|
2.8%
1/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/18 • Upto 44 Weeks
|
2.8%
1/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Gastrointestinal disorders
DIARRHEA
|
0.00%
0/18 • Upto 44 Weeks
|
2.8%
1/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Gastrointestinal disorders
DYSPEPSIA
|
0.00%
0/18 • Upto 44 Weeks
|
2.8%
1/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Gastrointestinal disorders
PROCTITIS
|
0.00%
0/18 • Upto 44 Weeks
|
2.8%
1/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
General disorders
FATIGUE
|
0.00%
0/18 • Upto 44 Weeks
|
2.8%
1/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
General disorders
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS ( irritation and bleeding)
|
0.00%
0/18 • Upto 44 Weeks
|
2.8%
1/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Infections and infestations
ANORECTAL INFECTION
|
0.00%
0/18 • Upto 44 Weeks
|
2.8%
1/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Infections and infestations
OTITIS MEDIA
|
0.00%
0/18 • Upto 44 Weeks
|
2.8%
1/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
|
Psychiatric disorders
INSOMNIA
|
0.00%
0/18 • Upto 44 Weeks
|
2.8%
1/36 • Upto 44 Weeks
|
0.00%
0/37 • Upto 44 Weeks
|
0.00%
0/5 • Upto 44 Weeks
|
0.00%
0/14 • Upto 44 Weeks
|
0.00%
0/13 • Upto 44 Weeks
|
Additional Information
Dr Himanshu Joshi, MBBS, MPH, PhD (Assistant Professor)
AMC Statistical Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place