Cervical Intraepithelial Neoplasia Clinical Trial
— TOPICOfficial title:
TOPical Imiquimod Treatment of High-grade Cervical Intraepithelial Neoplasm: a Randomized Controlled Trial.
Verified date | June 2016 |
Source | Maastricht University Medical Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Rationale:
Cervical Intraepithelial Neoplasia (CIN) is the premalignant condition of cervical cancer.
High grade CIN (CIN 2-3) is currently treated by large loop excision of the transformation
zone (LLETZ). This treatment has potential complications, such as hemorrhage, infection and
preterm birth in subsequent pregnancies. For this reason, non-invasive therapies are needed.
Imiquimod (an immunomodulator) was proven effective in the treatment of HPV-related vulvar
intraepithelial neoplasia (VIN) and may also be effective in HPV-related CIN. [van Seters,
2012] However, the evidence is limited and study results are not consistent. [Grimm, 2012;
Pachman, 2012; Lin, 2012]
Objectives:
Primary objectives: (1) to investigate the efficacy of imiquimod 5% cream for the treatment
of CIN2-3 lesions and (2) to develop biomarker panels to predict clinical response to
imiquimod therapy.
Secondary objectives: to assess side effects of imiquimod treatment and LLETZ, disease
recurrence and quality of life.
Hypothesis:
The investigators hypothesize that imiquimod will be an effective treatment modality in
approximately 50-75% of CIN lesions treated without surgical intervention.
Study design:
Single-centre randomized controlled intervention trial.
Study population:
140 women with a histological diagnosis of CIN2-3, equally divided over two study arms.
Intervention:
Patients will be randomized into one of two arms:
1. Imiquimod treatment arm. Patients in this group are treated by a 16-week regime of
imiquimod 5% cream.
2. Standard treatment arm. LLETZ will be performed on patients in this group.
Colposcopy with diagnostic biopsies will be performed after 10 weeks for the imiquimod
treatment arm. In case progressive disease, the treatment will be ended and appropriate
surgical excision will be performed. Treatment efficacy will be evaluated after 20 weeks, by
colposcopy with diagnostic biopsies. A histological biomarker panel will be developed,
consisting of markers representing both host and viral factors.
Main study parameters/endpoints:
The primary endpoint of the study is regression-or-not of CIN2-3, defined as CIN1 or less at
the colposcopy at 20 weeks for the imiquimod arm and PAP 1 cytology at 6 months for the LLETZ
group.
Status | Terminated |
Enrollment | 9 |
Est. completion date | June 2016 |
Est. primary completion date | June 2016 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Female |
Age group | 18 Years and older |
Eligibility |
Inclusion criteria: - newly diagnosed high grade CIN lesions (CIN 2-3), histologically confirmed - age 18 years or older Exclusion criteria: - immunodeficiency - pregnancy or lactation - legally incapability - history of histologically conformed high-grade CIN |
Country | Name | City | State |
---|---|---|---|
Netherlands | Maastricht University Medical Centre | Maastricht |
Lead Sponsor | Collaborator |
---|---|
Maastricht University Medical Center | MEDA Pharma GmbH & Co. KG |
Netherlands,
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* Note: There are 16 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Treatment efficacy: histological disease regression | Defined as following: for imiquimod treatment arm: CIN1 or less in diagnostic biopsies at colposcopy at 20 weeks for LLETZ arm: PAP 1 at 6 months follow-up |
20 weeks | |
Primary | Baseline biomarker profile predicting clinical response to imiquimod treatment | The biomarker profiles will consist of markers reflecting host and viral factors, including HPV-genotype, markers of immunologic response (CD4, CD8, CD25, CD138, Fox p3) and markers of cell cycle processes (Rb, p53, Ki67, CK 13/14, IMP3). | 20 weeks | |
Secondary | Prevalence and severity of side effects of imiquimod and LLETZ treatment | The prevalence and severity of side effects of imiquimod and LLETZ treatment, as documented according to Common Terminology Criteria for Adverse Events guidelines. | 6 weeks, 10 weeks, 14 weeks and 20 weeks for imiquimod treatment and 6 weeks for LLETZ treatment | |
Secondary | Quality of life for all treatment groups. | Assessed by the following questionnaires: RAND 36, EORTC QLQ-C30 and EORTC QLQ-CX24. | Baseline, 20 weeks and 1 year | |
Secondary | Disease recurrence for all treatment groups. | Defined as abnormal cervical cytology. | 6, 12 and 24 months |
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