Primary objectives: Evaluation of the efficacy of imiquimod 5% cream compared to treatment with Large Loop excision of the transformation zone (LLETZ) for recurrent/residual CIN.Secondary objectives: evaluation of the effect of treatments on HPV DNA…
ID
Source
Brief title
Condition
- Other condition
- Therapeutic and nontherapeutic effects (excl toxicity)
- Obstetric and gynaecological therapeutic procedures
Synonym
Health condition
gynaecologische afwijkingen, CIN afwijkingen
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome: Reduction to normal cytology 6 months after treatment.
Secondary outcome
Secondary outcomes: Reduction to no dysplasia 10 weeks after the treatment in
the imiquimod group, presence or absence of HPV DNA in CIN lesions before and
after treatment, tolerability to the treatment, quality of life and durability
of the clinical response at 6, 12 and 24 months after the final treatment, time
between treatment and conversion from hrHPV positivity, acceptability of
self-sampling method with urine.
Background summary
Cervical dysplasia is caused by Human Papillomavirus (HPV) and most common in
women of reproductive age. Current treatment of moderate to severe dysplasia is
surgical and aimed at eliminating the affected part of the transformation zone.
However, 15% of women treated for high grade cervical intraepithelial neoplasia
(CIN grade 2 or 3) develop residual or recurrent CIN grade 2 or 3 or cervical
cancer after surgical excision. Women who are HPV positive after surgery are at
higher risk for treatment failure. This could raise the question if these
patients need medical treatment that treats the HPV infection as an alternative
to surgical treatment.
Study objective
Primary objectives: Evaluation of the efficacy of imiquimod 5% cream compared
to treatment with Large Loop excision of the transformation zone (LLETZ) for
recurrent/residual CIN.
Secondary objectives: evaluation of the effect of treatments on HPV DNA
presence in CIN lesions, evaluation of tolerability of Imiquimod in CIN
lesions, evaluation of quality of life and establishment of long term
recurrence rate of CIN lesions and HPV status, time between treatment and
conversion from hrHPV positivity, acceptability of self-sampling method with
urine.
Study design
This study is designed as a multicentre, non-inferiority randomized single
blinded study.
Intervention
Included patients will be randomized to receive either 5% imiquimod cream
intravaginal or LLETZ. In the Imiquimod group, Imiquimod will be inserted three
times a week intravaginally for a period of 16 weeks using a vaginal
applicator. Clinical assessment will take place every 4 weeks during treatment
for the Imiquimod group. Ten weeks after the end of imiquimod treatment a
biopsy will be taken for treatment response. In case of progressive disease a
LLETZ will be performed. At 6, 12 and 24 months after the end of treatment
cytology will be taken for follow up. Subsequently, results of the first
cytology taken by the Dutch screening program for cervical cancer will be
collected. The LLETZ group will be treated according the current guidelines, so
cytology will be taken at 6, 12 and 24 months after the treatment. Also their
results from the first outcome of the screening program will be collected.
Study burden and risks
All patients in imiquimod group will be seen 8 times at the clinic for the
study. Adverse events and symptoms will be evaluated during these visits. Risk
and burden are linked to protocol procedures, such as biopsy sampling. Although
these are routine procedures, carried out by medical qualified personnel, they
may cause side effects or discomfort to the subject. However, it is expected
that these procedures will generally be well tolerated. The advantage of
imiquimod treatment will be that patients do not have to undergo a surgical
procedure in treating the CIN lesion and clearing the HPV virus.
The risk of disease progression in the imiquimod treatment arm is minimalized
in the study protocol by frequent re-examinations and biopsies.
There will be self sampling of urine, this will be taken place at home, so
minimalize the burden for the patient.
`s Gravendijkwal 230
Rotterdam 3015 CE
NL
`s Gravendijkwal 230
Rotterdam 3015 CE
NL
Listed location countries
Age
Inclusion criteria
- Histologically proven CIN2 or CIN 3, without invasion after previous surgical treatment at least 6 months before diagnosis
- Histologically proven persistent CIN 1 after previous surigcal treament at least 6 months before diagnosis. Persistent CIN 1 is defined as CIN 1 at least persistent for 6 months and proven with histology
- The patient is willing to use a medically acceptable method of contraception throughout the study
- Women older than 18 years of age
Exclusion criteria
- Pregnancy or lactation
- (Micro-)invasive carcinoma
- Past history of cervical cancer
- Hypersensitivity of any components of the formulation
- History of psoriasis or other inflammatory dermatosis of the vulva
- Immunodeficiency or treatment with immunosuppressive medication
- Insufficient understanding of the Dutch or English language
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-002308-10-NL |
| ClinicalTrials.gov | NCT02669459 |
| CCMO | NL53792.078.15 |