Brief Title
Imiquimod Treatment of High-grade CIN
Official Title
TOPical Imiquimod Treatment of High-grade Cervical Intraepithelial Neoplasia, a Multicenter, Open-label, Non-randomized, Controlled Study (TOPIC-3 Study)
Brief Summary
This multi-center, open-label, non-randomized controlled intervention study aims to
investigate the treatment efficacy, side-effects and quality of life associated with
imiquimod treatment of high-grade CIN lesions, as an alternative to surgical treatment by
Large Loop Excision of the Transformation Zone (LLETZ). Non-surgical treatment may prevent
side-effects associated with surgical treatment, such as premature birth in subsequent
pregnancies. The study hypothesis is that approximately 75% of patients with high-grade CIN
will be adequately treated with imiquimod.
120 women with a histological diagnosis of CIN2 or CIN3 will be included and allocated to one
of two treatment arms according to their preference:
1. Imiquimod treatment arm(60 patients). Patients in this group are treated with vaginal
imiquimod 5% cream during 16 weeks.
2. Standard treatment arm (60 patients). Patients in this group will undergo LLETZ
treatment.
Detailed Description
Cervical Intraepithelial Neoplasia (CIN) is the premalignant condition of cervical cancer.
The standard treatment of histologically confirmed CIN2-3 is surgical excision by large loop
excision of the transformation zone (LLETZ). This procedure has potential complications, such
as hemorrhage, infection and preterm birth in subsequent pregnancies. For this reason,
non-invasive therapies are needed. Imiquimod cream has been studied as a non-invasive
treatment alternative in high-grade CIN, but evidence on treatment efficacy is limited and
evidence on disease recurrence and quality of life during and after treatment is lacking. One
RCT has been performed and shows that treatment of high-grade CIN with vaginal imiquimod
cream leads to disease regression in 73%. Side-effects were generally mild, but common. A
recent survey among gynecologists and a patient preference study indicate that imiquimod
treatment of high-grade CIN is mainly preferred by a selected population of women with a
future pregnancy wish. These women accept a lower treatment efficacy and higher rates of
side-effects from imiquimod treatment in order to prevent future preterm birth caused by
LLETZ treatment. Ideally, those women with a high probability of successful treatment would
be selected.
The objective of this study is to investigate the treatment efficacy, side-effects and
quality of life associated with imiquimod treatment of high-grade CIN lesions in a selected
population of patients who prefer imiquimod treatment instead of LLETZ. The study also aims
to identify predictive biomarkers clinical response to imiquimod treatment, in order to
select patients in which good treatment response is expected.
The study design is a multicenter, open-label, non-randomized controlled intervention study.
120 women with a histological diagnosis of CIN2 or CIN3 will be included and allocated to one
of two treatment arms according to their preference:
1. Imiquimod treatment arm(60 patients). Patients in this group are treated with vaginal
imiquimod 5% cream during 16 weeks.
2. Standard treatment arm (60 patients). Patients in this group will undergo LLETZ
treatment.
A control colposcopy will be performed after 10 weeks for the imiquimod group. In case of
progressive disease, the treatment will be ended and LLETZ will be performed as treatment.
For patients in which the treatment is continued, treatment efficacy will be evaluated after
20 weeks, by colposcopy with diagnostic biopsies. Statistical analysis will be performed
based on an intention-to-treat analysis.
The primary study endpoints are:
- Treatment efficacy of imiquimod and LLETZ treatment, defined as regression to CIN1 or
less after 20 weeks for imiquimod and no need for additional therapy within 6 months for
LLETZ treatment.
- Identification of predictive biomarkers for the efficacy of imiquimod treatment in the
individual patient, based on biomarkers reflecting host, virus and cellular factors.
Secondary study endpoints are:
- Side effects of imiquimod therapy and LLETZ therapy.
- Disease recurrence at 6, 12 and 24 months follow-up.
- Quality of life (QoL) before, during and after treatment.
Study Type
Interventional
Primary Outcome
Treatment efficacy of imiquimod 5% cream for the treatment of CIN2-3 lesions, compared to LLETZ treatment, in selected populations.
Secondary Outcome
Side effects of imiquimod therapy and LLETZ therapy.
Condition
Cervical Intraepithelial Neoplasia
Intervention
Imiquimod
Study Arms / Comparison Groups
Imiquimod treatment arm
Description: Treatment by vaginal imiquimod cream during 16 weeks.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
120
Start Date
November 2016
Completion Date
December 2020
Primary Completion Date
July 2018
Eligibility Criteria
Inclusion Criteria:
- de novo CIN2 or CIN3 lesion, histologically confirmed by diagnostic biopsy
- age of 18 years or older
Exclusion Criteria:
- previous histologically confirmed high-grade CIN (CIN 2-3)
- concomitant vulvar and/or vaginal intraepithelial neoplasia
- previous cervical malignancy
- current malignant disease
- immunodeficiency (including HIV/AIDS and immunodepressive medication)
- pregnancy or lactation
- legal incapability
Gender
Female
Ages
18 Years - 99 Years
Accepts Healthy Volunteers
No
Contacts
A.J. Kruse, MD, PhD, ,
Location Countries
Netherlands
Location Countries
Netherlands
Administrative Informations
NCT ID
NCT02917746
Organization ID
NL 57849.068.16
Responsible Party
Sponsor
Study Sponsor
Maastricht University Medical Center
Collaborators
Clinical Trial Center Maastricht B.V.
Study Sponsor
A.J. Kruse, MD, PhD, Study Director, Maastricht University Medical Center
Verification Date
May 2018