Trial Outcomes & Findings for Topical Fluorouracil and Imiquimod in Treating Patients With High-Grade Cervical Intraepithelial Neoplasia (NCT NCT03196180)
NCT ID: NCT03196180
Last Updated: 2025-04-08
Results Overview
Feasibility is evaluated based on safety and tolerability of the study intervention. For safety, the study assessed the number of participants experiencing the specified adverse events defined as Grade 2 or greater toxicity (or Grade 1 toxicity of any genital lesion (blisters, ulcerations, or pustules)) that is possibly, probably, or definitely related and lasts for more than 5 days. For tolerability, the study assessed the number of participants who were not able to apply at least 50% of the treatment due to the specified adverse events.
Recruitment status
COMPLETED
Study phase
EARLY_PHASE1
Target enrollment
13 participants
Primary outcome timeframe
Up to 22 weeks
Results posted on
2025-04-08
Participant Flow
Participant milestones
| Measure |
Treatment (Topical Fluorouracil, Imiquimod)
Patients receive once-weekly intravaginal application of 5-fluorouracil and imiquimod used on alternating weeks for 8 to 16 weeks.
Imiquimod: Given intravaginally
Topical Fluorouracil: Given intravaginally
|
|---|---|
|
Overall Study
STARTED
|
13
|
|
Overall Study
COMPLETED
|
11
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Topical Fluorouracil and Imiquimod in Treating Patients With High-Grade Cervical Intraepithelial Neoplasia
Baseline characteristics by cohort
| Measure |
Treatment (Topical Fluorouracil, Imiquimod)
n=13 Participants
Patients receive once-weekly intravaginal application of 5-fluorouracil and imiquimod used on alternating weeks for 8 to 16 weeks.
Imiquimod: Given intravaginally
Topical Fluorouracil: Given intravaginally
|
|---|---|
|
Age, Continuous
|
27 years
STANDARD_DEVIATION 4 • n=93 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
13 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Up to 22 weeksFeasibility is evaluated based on safety and tolerability of the study intervention. For safety, the study assessed the number of participants experiencing the specified adverse events defined as Grade 2 or greater toxicity (or Grade 1 toxicity of any genital lesion (blisters, ulcerations, or pustules)) that is possibly, probably, or definitely related and lasts for more than 5 days. For tolerability, the study assessed the number of participants who were not able to apply at least 50% of the treatment due to the specified adverse events.
Outcome measures
| Measure |
Treatment (Topical Fluorouracil, Imiquimod)
n=13 Participants
Patients receive topical fluorouracil intravaginally via applicator at weeks 1, 3, 5, 7, 9, 11, 13, and 15 and imiquimod intravaginally via applicator at weeks 2, 4, 6, 8, 10, 12, 14, and 16. Patients who are menstruating will delay application until the end of the menstrual cycle.
Imiquimod: Given intravaginally
Topical Fluorouracil: Given intravaginally
|
|---|---|
|
Feasibility of Intravaginal Use 5-FU and Imiquimod on Alternating Weeks in Women With Biopsy Confirmed High Grade Cervical Squamous Intraepithelial Lesions.
Tolerability
|
1 Participants
|
|
Feasibility of Intravaginal Use 5-FU and Imiquimod on Alternating Weeks in Women With Biopsy Confirmed High Grade Cervical Squamous Intraepithelial Lesions.
Safety
|
4 Participants
|
SECONDARY outcome
Timeframe: At end of study visit (4-6 weeks after the last agent application)Population: Participants who were HR-HPV negative at baseline were excluded from the analysis
The response will be reported along with their 95% confidence intervals. Response is defined as histologic regression from high-grade lesions to low-grade- or no lesions and clearance of HR-HPV detection between baseline and end of study.
Outcome measures
| Measure |
Treatment (Topical Fluorouracil, Imiquimod)
n=10 Participants
Patients receive topical fluorouracil intravaginally via applicator at weeks 1, 3, 5, 7, 9, 11, 13, and 15 and imiquimod intravaginally via applicator at weeks 2, 4, 6, 8, 10, 12, 14, and 16. Patients who are menstruating will delay application until the end of the menstrual cycle.
Imiquimod: Given intravaginally
Topical Fluorouracil: Given intravaginally
|
|---|---|
|
Response to Intravaginal 5-FU and Imiquimod Defined as Histologic Regression and Clearance of High-risk Human Papilloma Virus (HR-HPV)
|
40 percentage of participants
Interval 12.0 to 74.0
|
SECONDARY outcome
Timeframe: At end of study visit (4-6 weeks after the last agent application)Population: Participants positive for a given HPV genotype at baseline were assessed for the clearance of this genotype at the end of study.
The type-specific HR-HPV clearance will be reported along with their 95% confidence intervals.
Outcome measures
| Measure |
Treatment (Topical Fluorouracil, Imiquimod)
n=12 Participants
Patients receive topical fluorouracil intravaginally via applicator at weeks 1, 3, 5, 7, 9, 11, 13, and 15 and imiquimod intravaginally via applicator at weeks 2, 4, 6, 8, 10, 12, 14, and 16. Patients who are menstruating will delay application until the end of the menstrual cycle.
Imiquimod: Given intravaginally
Topical Fluorouracil: Given intravaginally
|
|---|---|
|
Type Specific Human Papillomavirus (HPV) Clearance
HPV16
|
75 percentage of participants
Interval 19.0 to 99.0
|
|
Type Specific Human Papillomavirus (HPV) Clearance
HPV31
|
50 percentage of participants
Interval 1.0 to 99.0
|
|
Type Specific Human Papillomavirus (HPV) Clearance
HPV35
|
100 percentage of participants
Interval 3.0 to 100.0
|
|
Type Specific Human Papillomavirus (HPV) Clearance
HPV39
|
0 percentage of participants
Interval 0.0 to 98.0
|
|
Type Specific Human Papillomavirus (HPV) Clearance
HPV51
|
0 percentage of participants
Interval 0.0 to 84.0
|
|
Type Specific Human Papillomavirus (HPV) Clearance
HPV52
|
75 percentage of participants
Interval 19.0 to 99.0
|
|
Type Specific Human Papillomavirus (HPV) Clearance
HPV56
|
0 percentage of participants
Interval 0.0 to 98.0
|
|
Type Specific Human Papillomavirus (HPV) Clearance
HPV66
|
50 percentage of participants
Interval 1.0 to 99.0
|
|
Type Specific Human Papillomavirus (HPV) Clearance
HPV68
|
100 percentage of participants
Interval 16.0 to 100.0
|
SECONDARY outcome
Timeframe: Baseline to up to end of study visit (4-6 weeks after last agent application)Population: Participants with data at both baseline and end of study for a given biomarker were included in the analysis.
For each biomarker, the mean change of log transformed data and the associated standard deviation will be reported. Will measure the innate (IFN-alpha2), immune mediating (IFN-gamma, IL-10, IL-12), and pro-inflammatory (IL-1alpha, -1beta, -6, -8, MIP-1alpha, TNF) cytokine.
Outcome measures
| Measure |
Treatment (Topical Fluorouracil, Imiquimod)
n=12 Participants
Patients receive topical fluorouracil intravaginally via applicator at weeks 1, 3, 5, 7, 9, 11, 13, and 15 and imiquimod intravaginally via applicator at weeks 2, 4, 6, 8, 10, 12, 14, and 16. Patients who are menstruating will delay application until the end of the menstrual cycle.
Imiquimod: Given intravaginally
Topical Fluorouracil: Given intravaginally
|
|---|---|
|
Change in Expression of Biomarkers of Local Immune Activation (Cytokines) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
IFN-alpha 2
|
-0.29 log pg/ml
Standard Deviation 1.49
|
|
Change in Expression of Biomarkers of Local Immune Activation (Cytokines) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
IFN-gamma
|
0.16 log pg/ml
Standard Deviation 0.81
|
|
Change in Expression of Biomarkers of Local Immune Activation (Cytokines) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
IL-1 alpha
|
-0.55 log pg/ml
Standard Deviation 1.01
|
|
Change in Expression of Biomarkers of Local Immune Activation (Cytokines) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
IL-1 beta
|
-0.15 log pg/ml
Standard Deviation 1.84
|
|
Change in Expression of Biomarkers of Local Immune Activation (Cytokines) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
IL-6
|
-0.84 log pg/ml
Standard Deviation 1.94
|
|
Change in Expression of Biomarkers of Local Immune Activation (Cytokines) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
IL-8
|
-0.16 log pg/ml
Standard Deviation 2.63
|
|
Change in Expression of Biomarkers of Local Immune Activation (Cytokines) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
IL-12
|
0.15 log pg/ml
Standard Deviation 0.95
|
|
Change in Expression of Biomarkers of Local Immune Activation (Cytokines) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
IL-13
|
-0.53 log pg/ml
Standard Deviation 1.11
|
|
Change in Expression of Biomarkers of Local Immune Activation (Cytokines) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
MIP-1 alpha
|
0.66 log pg/ml
Standard Deviation 0.77
|
|
Change in Expression of Biomarkers of Local Immune Activation (Cytokines) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
TNF alpha
|
-0.01 log pg/ml
Standard Deviation 1.99
|
SECONDARY outcome
Timeframe: Baseline to up to end of study visit (4-6 weeks after last agent application)Population: Participants with data at both baseline and end of study for a given biomarker were included in the analysis.
For each biomarker, the mean change of log transformed data and the associated standard deviation will be reported. TLR messenger ribonucleic acid expression is normalized by the housekeeping genes and does not have a unit of measure.
Outcome measures
| Measure |
Treatment (Topical Fluorouracil, Imiquimod)
n=12 Participants
Patients receive topical fluorouracil intravaginally via applicator at weeks 1, 3, 5, 7, 9, 11, 13, and 15 and imiquimod intravaginally via applicator at weeks 2, 4, 6, 8, 10, 12, 14, and 16. Patients who are menstruating will delay application until the end of the menstrual cycle.
Imiquimod: Given intravaginally
Topical Fluorouracil: Given intravaginally
|
|---|---|
|
Change in Expression of Biomarkers of Local Immune Activation (Toll Like Receptors (TLRs)) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
TLR2
|
0.90 gene expression level
Standard Deviation 2.16
|
|
Change in Expression of Biomarkers of Local Immune Activation (Toll Like Receptors (TLRs)) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
TLR3
|
0.75 gene expression level
Standard Deviation 4.26
|
|
Change in Expression of Biomarkers of Local Immune Activation (Toll Like Receptors (TLRs)) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
TLR4
|
0.86 gene expression level
Standard Deviation 1.84
|
|
Change in Expression of Biomarkers of Local Immune Activation (Toll Like Receptors (TLRs)) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
TLR7
|
2.20 gene expression level
Standard Deviation 1.36
|
|
Change in Expression of Biomarkers of Local Immune Activation (Toll Like Receptors (TLRs)) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
TLR9
|
0.95 gene expression level
Standard Deviation 4.43
|
Adverse Events
Treatment (Topical Fluorouracil, Imiquimod)
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment (Topical Fluorouracil, Imiquimod)
n=13 participants at risk
Patients receive once-weekly intravaginal application of 5-fluorouracil and imiquimod used on alternating weeks for 8 to 16 weeks.
Imiquimod: Given intravaginally
Topical Fluorouracil: Given intravaginally
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
7.7%
1/13 • 14-22 weeks
|
|
Gastrointestinal disorders
Pain - Lower abdominal
|
15.4%
2/13 • 14-22 weeks
|
|
General disorders
Fever
|
7.7%
1/13 • 14-22 weeks
|
|
General disorders
Flu like symptoms
|
7.7%
1/13 • 14-22 weeks
|
|
General disorders
Other
|
15.4%
2/13 • 14-22 weeks
|
|
Infections and infestations
Bacterial vaginosis
|
7.7%
1/13 • 14-22 weeks
|
|
Infections and infestations
Candida
|
7.7%
1/13 • 14-22 weeks
|
|
Infections and infestations
Upper respiratory infection
|
38.5%
5/13 • 14-22 weeks
|
|
Investigations
Weight gain
|
23.1%
3/13 • 14-22 weeks
|
|
Investigations
Weight loss
|
15.4%
2/13 • 14-22 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.7%
1/13 • 14-22 weeks
|
|
Nervous system disorders
Headache
|
30.8%
4/13 • 14-22 weeks
|
|
Renal and urinary disorders
Dysuria
|
7.7%
1/13 • 14-22 weeks
|
|
Reproductive system and breast disorders
Cervical erythema
|
7.7%
1/13 • 14-22 weeks
|
|
Reproductive system and breast disorders
Cervical friability
|
7.7%
1/13 • 14-22 weeks
|
|
Reproductive system and breast disorders
Dysmenorrhea/cramping with menses
|
15.4%
2/13 • 14-22 weeks
|
|
Reproductive system and breast disorders
Dyspareunia
|
7.7%
1/13 • 14-22 weeks
|
|
Reproductive system and breast disorders
Metrorrhagia
|
7.7%
1/13 • 14-22 weeks
|
|
Reproductive system and breast disorders
Pain - Pelvic
|
46.2%
6/13 • 14-22 weeks
|
|
Reproductive system and breast disorders
Pain - Vagina
|
61.5%
8/13 • 14-22 weeks
|
|
Reproductive system and breast disorders
Postcoital bleeding
|
7.7%
1/13 • 14-22 weeks
|
|
Reproductive system and breast disorders
Unexplained infrequent bleeding
|
30.8%
4/13 • 14-22 weeks
|
|
Reproductive system and breast disorders
Vaginal abrasions
|
7.7%
1/13 • 14-22 weeks
|
|
Reproductive system and breast disorders
Vaginal discharge as observed by clinician
|
7.7%
1/13 • 14-22 weeks
|
|
Reproductive system and breast disorders
Vaginal erythema
|
7.7%
1/13 • 14-22 weeks
|
|
Reproductive system and breast disorders
Vaginal discharge by participant report
|
53.8%
7/13 • 14-22 weeks
|
|
Reproductive system and breast disorders
Vaginal lesions
|
23.1%
3/13 • 14-22 weeks
|
|
Reproductive system and breast disorders
Vulvar/vaginal itching
|
38.5%
5/13 • 14-22 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
15.4%
2/13 • 14-22 weeks
|
|
Vascular disorders
Hypertension
|
38.5%
5/13 • 14-22 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60