Cervical Intraepithelial Neoplasia Grade 2/3Early Phase 1NCT03196180
Topical Fluorouracil and Imiquimod in Treating Patients With High-Grade Cervical Intraepithelial Neoplasia
A Early Phase 1 study testing Imiquimod and Topical Fluorouracil in people with Cervical Intraepithelial Neoplasia Grade 2/3 and Cervical Squamous Cell Carcinoma In Situ, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This early phase I clinical trial studies the side effects of topical fluorouracil and imiquimod ointment in treating patients with high-grade cervical intraepithelial neoplasia. Topical fluorouracil may kill precancerous cells. Imiquimod ointment may stimulate the immune system. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Cervical Intraepithelial Neoplasia Grade 2/3, Cervical Squamous Cell Carcinoma In Situ, Cervical Squamous Intraepithelial Neoplasia 2
- What is being tested?
- Imiquimod and Topical Fluorouracil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Oct 2019to 2 Aug 2024
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women with biopsy confirmed high grade cervical squamous intraepithelial lesions (i.e., cervical squamous intraepithelial neoplasia 3 [CIN3] lesions, and cervical squamous epithelial neoplasia 2 [CIN2] lesions with diagnosis confirmed by positive p16 immunohistochemistry staining) within 12 weeks of baseline visit
- Karnofsky >= 70%
- Leukocytes >= 3,000/microliter
- Absolute neutrophil count >= 1,500/microliter
- Platelets >= 100,000/microliter
- Serum creatinine =< the upper institutional limits
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- Participants must have a negative human immunodeficiency virus (HIV) antibody/antigen test and negative Chlamydia (C.) trachomatis/Neisseria (N.) gonorrhea nucleic acid amplification test (NAAT)
- Agree to use an effective form of contraception; the effects of intravaginal 5-fluorocuracil and imiquimod on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because 5- fluorouracil is known to be teratogenic, women of child-bearing potential must agree to use adequate dual methods of contraception (hormonal method of birth control, intrauterine device, or tubal ligation - plus condoms) or abstinence prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Women treated previously with 5-fluorouracil or imiquimod or other medications for high-grade squamous intraepithelial lesions will be excluded from the study
- Concurrent vaginal, vulvar, anal lesions or symptomatic infections
- Pregnant or planning pregnancy within the next 6 months, or breastfeeding; pregnant women are excluded from this study because 5-fluorouracil is an antimetabolite with the potential for teratogenic effects; because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with 5-fluorouracil, breastfeeding should be discontinued if the mother is treated with 5-fluorouracil
- Inability to speak or read English or Spanish
- Prior hysterectomy
- Use of anticoagulant medications
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- Subjects who have a known immunocompromised condition (HIV positive [+], use of immunosuppressive medications or systemic steroids, organ transplant recipients) or autoimmune conditions (e.g. psoriasis, rheumatoid arthritis or other known autoimmune conditions)
- Evidence of invasive anal, vulva, vaginal, or cervical carcinoma; prior loop electrosurgical excision procedure (LEEP) or ablative treatment within 6 months prior to study entry; other invasive malignancies, with the exception of non-melanoma skin cancer, within the last 5 years
- Pathologic findings consistent with
- Atypical endometrial cells or serious glandular-cell atypia (atypical glandular cells, favor neoplasia cytology diagnosis)
- Evidence of cervical carcinoma on Pap smear or biopsy
- More than two cervical quadrants of CIN 3 as visualized by colposcopy
- Nonvisual squamous columnar junction on colposcopy with no concurrent endocervical sampling performed
- Use of other investigational agents within 6 months prior to enrollment
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to 5-fluorouracil or imiquimod
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (other than human papilloma virus [HPV]), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Subjects with known partial or complete dihydropyrimidine dehydrogenase (DPD) enzyme deficiency
Trial locations and contacts
1 site in 1 country.
United States1 site
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
About this study
Official title: A Feasibility Trial of Alternating Intravaginal Application of 5-Fluorouracil and Imiquimod for Treatment of High-Grade Cervical Squamous Intraepithelial Lesions
This early phase I clinical trial studies the side effects of topical fluorouracil and imiquimod ointment in treating patients with high-grade cervical intraepithelial neoplasia. Topical fluorouracil may kill precancerous cells. Imiquimod ointment may stimulate the immune system. Applying topical fluorouracil and imiquimod ointment may cause fewer side effects and may be a better way to treat patients with precancerous cervical lesions.
Read the detailed description
PRIMARY OBJECTIVE:
- Assess feasibility, evaluated based on safety and tolerability, of a combination agent intervention (once-weekly self-administered intravaginal application of 5-fluorouracil alternating with once-weekly provider-applied imiquimod) for treatment of high-grade cervical squamous intraepithelial lesions.
SECONDARY OBJECTIVES:
- Assess efficacy of the combination agent intervention on cervical disease regression (endpoint based on histologic regression from high-grade lesions to low-grade or no lesions and clearance of high risk-human papillomavirus [HPV] detection) between baseline and study exit visits.
II. Assess efficacy of the combination agent intervention on genotype-specific HPV clearance between baseline and study exit visits.
III. Assess efficacy of the combination agent intervention on biomarkers of local immune activation (measurement of changes in expression of Toll-like receptors (TLR) and T-regulatory cells and the levels of innate, immune mediating and proinflammatory cytokines with intravaginal 5-fluorouracil [FU] and imiquimod) between baseline and study exit visits.
OUTLINE: This is a phase I, dose escalation study of imiquimod.
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.
After completion of study treatment, patients are followed up within 8 months.
- Conditions
- Cervical Intraepithelial Neoplasia Grade 2/3, Cervical Squamous Cell Carcinoma In Situ, Cervical Squamous Intraepithelial Neoplasia 2, High Grade Cervical Intraepithelial Neoplasia
- Being tested
- Imiquimod, Topical Fluorouracil
- Medical subject headings
- Uterine Cervical Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImiquimodDrug
Also called Aldara, R 837, S 26308, Zyclara
Given intravaginally
Topical FluorouracilDrug
Also called Actino-Hermal, Arumel, Carac, Cytosafe
Given intravaginally
| Study group | Role | What they receive |
|---|---|---|
| Treatment (topical fluorouracil, imiquimod) | Experimental | 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. Receives: Drug: Imiquimod; Drug: Topical Fluorouracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of Intravaginal Use 5-FU and Imiquimod on Alternating Weeks in Women With Biopsy Confirmed High Grade Cervical Squamous Intraepithelial Lesions.
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.
Measured: Up to 22 weeks
Secondary outcomes (4)
Response to Intravaginal 5-FU and Imiquimod Defined as Histologic Regression and Clearance of High-risk Human Papilloma Virus (HR-HPV)
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.
Measured: At end of study visit (4-6 weeks after the last agent application)
Type Specific Human Papillomavirus (HPV) Clearance
The type-specific HR-HPV clearance will be reported along with their 95% confidence intervals.
Measured: At end of study visit (4-6 weeks after the last agent application)
Change in Expression of Biomarkers of Local Immune Activation (Cytokines) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
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.
Measured: Baseline to up to end of study visit (4-6 weeks after last agent application)
Change in Expression of Biomarkers of Local Immune Activation (Toll Like Receptors (TLRs)) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
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.
Measured: Baseline to up to end of study visit (4-6 weeks after last agent application)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2017
- Study start15 Oct 2019
- Primary completion4 Nov 2020
- Study completion2 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cervical Intraepithelial Neoplasia Grade 2/3Studies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Lisa Rahangdale, Principal investigator, UNC Lineberger Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03196180
- Sponsor's protocol ID
- NCI-2017-01079
- Other IDs
- NCI-2017-01079, N01-CN-2012-00031, 1712088061, UAZ2016-08-02, N01CN00031, P30CA023074
- Status last verified
- Mar 2025
- First submitted
- 21 Jun 2017
- Last updated
- 8 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Feasibility Trial of Alternating Intravaginal Application of 5-Fluorouracil and Imiquimod for Treatment of High-Grade Cervical Squamous Intraepithelial Lesions
- ClinicalTrials.gov ID
- NCT03196180
- Acronym / sponsor ID
- NCI-2017-01079
- Conditions
- Cervical Intraepithelial Neoplasia Grade 2/3, Cervical Squamous Cell Carcinoma In Situ, Cervical Squamous Intraepithelial Neoplasia 2, High Grade Cervical Intraepithelial Neoplasia
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 15 Oct 2019 (actual)
- Primary completion
- 4 Nov 2020 (actual)
- Study completion
- 2 Aug 2024 (actual)
- First posted
- 22 Jun 2017 (actual)
- Results
- Posted 23 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This early phase I clinical trial studies the side effects of topical fluorouracil and imiquimod ointment in treating patients with high-grade cervical intraepithelial neoplasia. Topical fluorouracil may kill precancerous cells. Imiquimod ointment may stimulate the immune system. Applying topical fluorouracil and imiquimod ointment may cause fewer side effects and may be a better way to treat patients with precancerous cervical lesions.
Detailed description
PRIMARY OBJECTIVE:
- Assess feasibility, evaluated based on safety and tolerability, of a combination agent intervention (once-weekly self-administered intravaginal application of 5-fluorouracil alternating with once-weekly provider-applied imiquimod) for treatment of high-grade cervical squamous intraepithelial lesions.
SECONDARY OBJECTIVES:
- Assess efficacy of the combination agent intervention on cervical disease regression (endpoint based on histologic regression from high-grade lesions to low-grade or no lesions and clearance of high risk-human papillomavirus [HPV] detection) between baseline and study exit visits.
II. Assess efficacy of the combination agent intervention on genotype-specific HPV clearance between baseline and study exit visits.
III. Assess efficacy of the combination agent intervention on biomarkers of local immune activation (measurement of changes in expression of Toll-like receptors (TLR) and T-regulatory cells and the levels of innate, immune mediating and proinflammatory cytokines with intravaginal 5-fluorouracil [FU] and imiquimod) between baseline and study exit visits.
OUTLINE: This is a phase I, dose escalation study of imiquimod.
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.
After completion of study treatment, patients are followed up within 8 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (topical fluorouracil, imiquimod) | Experimental | Drug: Imiquimod, Drug: Topical FluorouracilPatients 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Women with biopsy confirmed high grade cervical squamous intraepithelial lesions (i.e., cervical squamous intraepithelial neoplasia 3 [CIN3] lesions, and cervical squamous epithelial neoplasia 2 [CIN2] lesions with diagnosis confirmed by positive p16 immunohistochemistry staining) within 12 weeks of baseline visit
- Karnofsky >= 70%
- Leukocytes >= 3,000/microliter
- Absolute neutrophil count >= 1,500/microliter
- Platelets >= 100,000/microliter
Key exclusion criteria (17 listed)
- Women treated previously with 5-fluorouracil or imiquimod or other medications for high-grade squamous intraepithelial lesions will be excluded from the study
- Concurrent vaginal, vulvar, anal lesions or symptomatic infections
- Pregnant or planning pregnancy within the next 6 months, or breastfeeding; pregnant women are excluded from this study because 5-fluorouracil is an antimetabolite with the potential for teratogenic effects; because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with 5-fluorouracil, breastfeeding should be discontinued if the mother is treated with 5-fluorouracil
- Inability to speak or read English or Spanish
- Prior hysterectomy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ImiquimodAlso: Aldara, R 837, S 26308, ZyclaraGiven intravaginally | Drug | Treatment (topical fluorouracil, imiquimod) |
| Topical FluorouracilAlso: Actino-Hermal, Arumel, Carac, CytosafeGiven intravaginally | Drug | Treatment (topical fluorouracil, imiquimod) |
Primary outcome
Feasibility of Intravaginal Use 5-FU and Imiquimod on Alternating Weeks in Women With Biopsy Confirmed High Grade Cervical Squamous Intraepithelial Lesions.
Time frame: Up to 22 weeks
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.
4 secondary outcomes
Response to Intravaginal 5-FU and Imiquimod Defined as Histologic Regression and Clearance of High-risk Human Papilloma Virus (HR-HPV)
Time frame: At end of study visit (4-6 weeks after the last agent application)
Type Specific Human Papillomavirus (HPV) Clearance
Time frame: At end of study visit (4-6 weeks after the last agent application)
Change in Expression of Biomarkers of Local Immune Activation (Cytokines) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
Time frame: Baseline to up to end of study visit (4-6 weeks after last agent application)
Change in Expression of Biomarkers of Local Immune Activation (Toll Like Receptors (TLRs)) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod
Time frame: Baseline to up to end of study visit (4-6 weeks after last agent application)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lisa Rahangdale principal investigator
UNC Lineberger Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Imiquimod and Topical Fluorouracil in people with Cervical Intraepithelial Neoplasia Grade 2/3 and Cervical Squamous Cell Carcinoma In Situ, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of Intravaginal Use 5-FU and Imiquimod on Alternating Weeks in Women With Biopsy Confirmed High Grade Cervical Squamous Intraepithelial Lesions. (time frame: Up to 22 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2025.