Page 175 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman
P. 175
Analysis of covariance will be used to compare group scores on these outcomes at 20 weeks and at 12 months, with adjustment for baseline scores.
Withdrawal of individual subjects and replacement
Subjects can leave the study at any time for any reason, without consequences. The investigator can decide to withdraw a subject from the study for medical reasons. Withdrawn individuals are not replaced by a new volunteer. Patients who withdraw from the study are offered the standard treatment of CIN, being a LLETZ procedure with standard follow up.
Ethical considerations and dissemination
The study was approved of by the Medical Ethical Committee of Maastricht University Hospital, University of Maastricht. The study will be performed according to the standards outlined in the Declaration of Helsinki. Ethics committee approval has been completed. Monitoring of the study is performed by a Data and Safety Monitoring Board, appointed by the Clinical Trial Center Maastricht. Adverse events are recorded and reported according to local protocol. Study results will be offered for publication in an international medical journal. Study results will be communicated to trial participants by mail, if agreed upon by the participant.
Substantial amendment
The current study protocol includes a substantial amendment to the original study protocol,
which consisted of three study arms: imiquimod treatment arm, LLETZ treatment arm and an 9 observational arm. The purpose of the observational arm was to assess spontaneous regression of a high-grade CIN and to develop a prognostic biomarker panel to predict spontaneous regression
of high-grade CIN. Patients in the observational arm underwent no treatment for a period of
maximum 20 weeks. Histological assessment of disease development was performed after 10
and 20 weeks by colposcopy with diagnostic biopsies. Inclusion of patients into the study was
hampered by the observational arm: patients declined the study because they wished to be
treated, rather than undergo observational management. The observational arm was removed
from the study.
Discussion
The development of a non-invasive treatment modality for high-grade CIN lesions may diminish complications as a result of surgical intervention. An earlier study indicates that imiquimod induces disease regression in 73%.[7, 13] Thus, imiquimod treatment may prevent surgical treatment in the majority of patients. The current study aims to test the treatment efficacy hypothesis as well as long term disease recurrence after treatment and clinical applicability of imiquimod treatment, defined as side effects and quality of life during and after treatment. Furthermore, it aims to develop a prediction model for clinical response to imiquimod treatment, based on histological biomarkers.
TOPIC trial
173