- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04859361
Comparison of Treatment of Cervical Intraepithelial Lesions With Imiquimod or LLETZ
Comparison of Conservative Treatment of Cervical Intraepithelial Lesions With Imiquimod With Standard Excisional Technique Using LLETZ: a Randomized Controlled Trial
Purpose: There are limited data on the success of conservative treatment of high-grade cervical squamous intraepithelial lesions (HSIL) with imiquimod directly compared to standard of treatment with LLETZ. LLETZ as standard treatment is possibly associated with premature labour, higher subfertility rate and a higher rate of spontaneous abortion. Since premature delivery is one of the most important causes of perinatal morbidity and mortality, alternative conservative methods for SIL treatment are constantly being evaluated. The immunomodulator imiquimod is one of the main target compounds for treating HSIL.
Primary objective: to establish the efficacy of treatment with imiquimod (experimental arm) and compare it to the standard treatment with LLETZ (control arm).
Secondary objective:
- incidence and severity of the side effects in both groups;
- need for treatment with LLETZ two years after primary treatment with imiquimod in the experimental arm or re-treatment with LLETZ two years after primary treatment with LLETZ in the control arm;
- modulatory effect of imiquimod on immunoregulatory molecules.
Study design: Single-centre randomized controlled intervention trial.
Study population: 104 women with HSIL (52 in each arm).
Intervention:
- randomization in two arms:
- Experimental arm (imiquimod): treatment for 16 weeks with 5% imiquimod.
- Control arm (LLETZ).
Successful treatment in the experimental arm is defined as absence of histological HSIL in diagnostic biopsies at 20-week follow-up (4 weeks after treatment completion) and in the control arm successful treatment is defined as absence of cytological HSIL in cytology 6 months after LLETZ (same as in our national guidelines).
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Maribor, Slovenia, 2000
- University Medical Centre Maribor
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- newly diagnosed and previously untreated HSIL in women aged 18 to 35 years or up to 40 years in case of nulliparity;
- satisfactory colposcopy (i.e., fully visible lesion and transformation zone);
- negative pregnancy test;
- safe contraception;
- signed, informed consent.
Exclusion Criteria:
- previously diagnosed HSIL or AIS;
- previous LLETZ or classical conisation;
- concomitant vulvar or vaginal lesion or neoplasia;
- other malignancies;
- insufficient colposcopy;
- pregnancy or lactation;
- known hypersensitivity to imiquimod;
- any known contraindications to immunotherapy;
- known HIV or acute or chronic hepatitis;
- immune deficiency;
- participation in any other ongoing clinical trial.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Treatment with imiquimod
Colposcopy with PAP smear and punch biopsy is scheduled at 10 weeks to rule out progression, and at 20 weeks to evaluate treatment success.
At 20 weeks, biopsies will be performed at the locations where lesions were previously present and additional biopsies will be performed on any visible lesions.
At 20 weeks, in case of disease progression or persistence, treatment with LLETZ will be offered.
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5% Imiquimod cream (1 sachet) will be administered via menstrual cup, before going to sleep, 3 times per week for 16 weeks.
Menstrual cup will be inserted in the vagina for a duration of 6-8 hours.
In case of severe side effects applications can be reduced to twice per week and if side effects are persistent, to once per week.
For maximum control of cervical disease, control colposcopy with a PAP smear and a punch biopsy will be scheduled at 10 weeks to rule out progression, and at 20 weeks after treatment initiation to evaluate treatment success.
At 20 weeks, biopsies will be performed at the locations where lesions were previously present, and if there are any new lesions present, additional biopsies will be performed.
In case of disease progression or persistence, treatment with LLETZ will be offered.
Other Names:
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Active Comparator: Treatment with LLETZ
Standard treatment will be scheduled after patients' first period.
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LLETZ will be performed in an outpatient setting with local anesthesia, using KLS Martin Maxium with loop devices ranging from 10 mm to 20 mm in size.
The excision will be performed using monopolar current with a cut frequency set to 100-150 W. Treatment success will be evaluated in accordance with our national guidelines 24 weeks after the procedure using a PAP smear with or without a punch biopsy.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment efficacy of 5% imiquimod cream for treatment of HSIL compared to standard treatment with LLETZ defined as absence of HSIL in both arms (histological in experimental arm and cytological in control arm).
Time Frame: 20 weeks after treatment initiation in experimental arm and 6 months after LLETZ in control arm.
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Defined as following:
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20 weeks after treatment initiation in experimental arm and 6 months after LLETZ in control arm.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Prevalence and severity of the side effects in both arms.
Time Frame: 10 weeks and 20 weeks after treatment initiation in experimental arm and 20 weeks after LLETZ in control arm.
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Incidence and severity of side effects scored by the 5th version of the Common Terminology Criteria for Adverse Events (CTCAE) guidelines.
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10 weeks and 20 weeks after treatment initiation in experimental arm and 20 weeks after LLETZ in control arm.
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Need for LLETZ or repeated LLETZ following primary treatment.
Time Frame: 2 years after primary treatment.
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The need for treatment with LLETZ two years after primary treatment with imiquimod in the experimental arm or re-treatment with LLETZ two years after primary treatment with LLETZ in the control arm
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2 years after primary treatment.
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Immunoregulatory effect of imiquimod.
Time Frame: 2 years after primary treatment.
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Modulatory effect of imiquimod on immunoregulatory molecules.
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2 years after primary treatment.
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Collaborators and Investigators
Publications and helpful links
General Publications
- Grimm C, Polterauer S, Natter C, Rahhal J, Hefler L, Tempfer CB, Heinze G, Stary G, Reinthaller A, Speiser P. Treatment of cervical intraepithelial neoplasia with topical imiquimod: a randomized controlled trial. Obstet Gynecol. 2012 Jul;120(1):152-9. doi: 10.1097/AOG.0b013e31825bc6e8.
- de Witte CJ, van de Sande AJ, van Beekhuizen HJ, Koeneman MM, Kruse AJ, Gerestein CG. Imiquimod in cervical, vaginal and vulvar intraepithelial neoplasia: a review. Gynecol Oncol. 2015 Nov;139(2):377-84. doi: 10.1016/j.ygyno.2015.08.018. Epub 2015 Aug 31.
- Koeneman MM, Kruse AJ, Kooreman LFS, Zur Hausen A, Hopman AHN, Sep SJS, Van Gorp T, Slangen BFM, van Beekhuizen HJ, van de Sande M, Gerestein CG, Nijman HW, Kruitwagen RFPM. TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC trial): study protocol for a randomized controlled trial. BMC Cancer. 2016 Feb 20;16:132. doi: 10.1186/s12885-016-2187-3.
- Jancar N, Mihevc Ponikvar B, Tomsic S. Cold-knife conisation and large loop excision of transformation zone significantly increase the risk for spontaneous preterm birth: a population-based cohort study. Eur J Obstet Gynecol Reprod Biol. 2016 Aug;203:245-9. doi: 10.1016/j.ejogrb.2016.06.005. Epub 2016 Jun 20.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2017-01-02
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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