Imiquimod Treatment of CIN Lesions

Summary

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.

Conditions

• Cervical Intraepithelial Neoplasia

Interventions

DRUG

Imiquimod

Imiquimod 5% cream will be administered in a vaginal applicator, containing 12,5 mg of imiquimod (one sachet). The cream will be self-administered three times per week, by use of a vaginal applicator.

PROCEDURE

LLETZ

Standard treatment consists of a LLETZ procedure, in which excision of the transformation zone and macroscopic lesions is performed by a monopolar loop electrode, under local anaesthesia. The excision is usually performed in two or three steps, depending on the size of the lesions.

Sponsors & Collaborators

• MEDA Pharma GmbH & Co. KG

  collaborator INDUSTRY

• Maastricht University Medical Center

  lead OTHER

Principal Investigators

• Arnold J Kruse, MD, PhD · Maastricht University Medical Center

• R.F.P.M. Kruitwagen, Professor · Maastricht University Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2014-12-31

Primary Completion

2016-06-30

Completion

2016-06-30

Countries

• Netherlands

Study Locations