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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

91 participants

Primary outcome timeframe

At week 20

Results posted on

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

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

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

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 20

Population: 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

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 20

Population: 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

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 20

Population: 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

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 20

Population: 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

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 20

Population: 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

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 20

Population: 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

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 20

Population: 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

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 20

Population: 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

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 44

Population: 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

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 20

Population: 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

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 20

Population: 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

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 16

Population: 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

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 weeks

Population: 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

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 44

Population: 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

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 20

Population: 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

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 20

Population: 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

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 weeks

Population: Per protocol

Count of HPV genotypes present at baseline but no longer detected at week 20.

Outcome measures

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

Serious events: 2 serious events
Other events: 2 other events
Deaths: 0 deaths

Arm B (Fluorouracil)- Up to 44 Weeks

Serious events: 4 serious events
Other events: 5 other events
Deaths: 0 deaths

Arm C (Observation)-Up to 20 Weeks

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Arm C (Observation) After Week 20-Imiquimod

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Arm C (Observation) After Week 20-Fluorouracil

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Arm C (Observation)- After Week 20, Not Crossed Over

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

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

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

Phone: 212-259-9635

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place