Condition category
Cancer
Date applied
28/03/2016
Date assigned
24/03/2017
Last edited
16/01/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
The cancer of the lining of the womb is the fourth most common female cancer in the UK. It is a multi-step disease that starts from accumulation of genetic changes (mutations) in normal womb followed by new growth and change leading to cancer. The pre-cancerous step includes overgrowth of the cells, where cells exhibit visible features of the abnormal growth. These features are described as “atypia”, an early process which may lead to cancer. Atypical abnormal growth can be diagnosed by examining tissue samples under the microscope (histological examination), but often doctors cannot agree on a definite diagnosis. Both underestimation and overestimation of the severity of the lesion are very common and there are no reliable predictors of cancer of the womb up to date. Recent research has shown that genetic analysis can provide more accurate prediction of atypical abnormal growth, whereas also, a genetic characterisation of cancer of the womb has been proposed, but still relatively little is known about genetic changes leading to initiation of atypical abnormal growth of cells. As well, hormonal imbalance detecting oestrogen dominance can be used as early preventative measure against development of cancer of the lining of the womb. Few case-control studies have examined the lifestyle and dietary correlations with the incidence of cancer of lining of the womb, however except for increased fat intake and obesity which shows a consistent positive correlation with the risk of developing cancer, there is insufficient data on lifestyle factors and incidence and its potential implication in terms of prevention of cancer of the lining of the womb. The aim of this study is to create comprehensive molecular analysis of atypical abnormal growth of cells in the lining of the womb against cancer, polyps and normal samples to identify candidate genes involved in the progression of atypical abnormal growth to cancer of the lining of the womb, and to compare findings with lifestyle parameters as well as blood hormones and microscopic examination results.

Who can participate?
Women aged 40 and older who have endometrial polyps and are awaiting surgery.

What does the study involve?
The study involves a comprehensive analysis of endometrial hyperplasia (EH) against endometrial cancer (EC), polyps and normal samples, and compare findings with diet and lifestyle parameters as well as biochemical and histological results. The research identifies candidate genes involved in the progression of EH to EC. Gene panel for detecting endometrial pre-cancerous disease will be developed. From these a risk prediction model is formed. Combination of lifestyle and diet assessment, biochemical analysis, histology and molecular biology evidence would enable clinical stratification of individuals into high-risk groups. Endometrial tissue samples (biopsies, polyps and resection specimens) and blood samples that are part of the normal clinical procedure are used. Blood samples are analysed for the level of female hormones and, also used, as control normal samples. Genetic information from tissue samples is extracted and analysed against already known cancer biomarkers using specialist equipment. For all enrolled participants, a food frequency and lifestyle questionnaire will be developed and completed, to include information such as dietary habits, BMI, family cancer history and etc.The data from the questionnaire is transformed into datasets and linked to the biochemical, genetic and histological findings, which will form a diagnostic assay.

What are the possible benefits and risks of participating?
Not provided at time of registration.

Where is the study run from?
Portsmouth Hospitals NHS Trust (UK)

When is the study starting and how long is it expected to run for?
June 2015 to June 2020

Who is funding the study?
League of Friends, Portsmouth Hospitals Charity (UK)

Who is the main contact?
1. Ms Iolia Akaev (Public)
iolia.akaev@port.ac.uk
2. Dr Siavash Rahimi (Scientific)

Trial website

Contact information

Type

Public

Primary contact

Ms Iolia Akaev

ORCID ID

http://orcid.org/0000-0002-4351-8147

Contact details

University of Portsmouth
School of Pharmacy and Biomedical Sciences
St. Michaels Building
White Swan Road
Portsmouth
PO1 2DT
United Kingdom
+44 7703 772086
iolia.akaev@port.ac.uk

Type

Scientific

Additional contact

Dr Siavash Rahimi

ORCID ID

http://orcid.org/0000-0002-8282-1480

Contact details

Portsmouth Hospitals NHS Trust
Queen Alexandra Hospital
Pathology Centre
Histopathology
Southwick Hill Road
Cosham
Portsmouth
PO6 3LY
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

PHT/2016/65

Study information

Scientific title

Predicting Risk of Endometrial Cancer: a multivariate prediction model with combination of lifestyle factors, clinical biochemistry, histological and genetic analysis

Acronym

PRECa

Study hypothesis

The combination of lifestyle and diet assessment, biochemical analysis, histology and molecular biology evidence enables clinical stratification of women, who are at high-risk for development of endometrium cancer. This combination could be early detected.

Ethics approval

Portsmouth Hospitals NHS Trust, University of Portsmouth

Study design

Prospective observational study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Condition

Endometrial cancer, endometrial hyperplasia, polyps and normal endometrium

Intervention

The project will involve a comprehensive analysis of endometrial hyperplasia (EH) against endometrial cancer (EC), polyps and normal samples, and compare findings with diet and lifestyle parameters as well as biochemical and histological results. The research will identify candidate genes involved in the progression of EH to EC. Gene panel for detecting endometrial pre-cancerous disease will be developed. From these a risk prediction model will be formed. Combination of lifestyle and diet assessment, biochemical analysis, histology and molecular biology evidence would enable clinical stratification of individuals into high-risk groups.

For the purpose of this study endometrial tissue samples (biopsies, polyps and resection specimens) and blood samples, that are part of the normal clinical procedure, will be used. Blood samples will be analysed for the level of female hormones and, also used, as control normal samples. Genetic information from tissue samples will be extracted and analysed against already known cancer biomarkers using specialist equipment. For all enrolled participants, a food frequency and lifestyle questionnaire will be developed and completed, to include information such as dietary habits, BMI, family cancer history and etc. The data from the questionnaire will be transformed into datasets and linked to the biochemical, genetic and histological findings, which will form a diagnostic assay.

Intervention type

Mixed

Phase

Drug names

Primary outcome measure

Lifestyle and diet assessment score, biochemical data, histological grade and genetic data will form a multivariate model. Generated data will be used for statistical modeling, where tests will be performed to determine differences between study cases. In order to determine which combination of tested variables best predicts EC, a stepwise discriminant analysis will be used.

Secondary outcome measures

Detection of differences in biochemical, histological and genetic results between studied conditions.

Overall trial start date

16/06/2015

Overall trial end date

15/06/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Women seen in Post Menopausal Clinic at Queen Alexandra Hospital
2. Ability to consent
3. Aged 40 years or over
4. Women with endometrial polyps
5. Women with prolapse awaiting surgery
6. Normal up to date smear
7. Normal endometrial sampling at screening
8. Not on prior endocrine treatment
9. No other/second cancer in the present or past

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

164

Participant exclusion criteria

Exclusion criteria as of 21/04/2017:
1. Previous hysterectomy
2. Breast cancer and breast cancer therapy
3. Taking systemic hormone replacement therapy or endocrine treatment

Original exclusion criteria:
1. Previous hysterectomy
2. Breast cancer and breast cancer therapy
3. Congenital/acquired uterine anomalies
4. Pelvic inflammatory disease, previous and active
5. Immunodeficiency or any chronic disease
6. Taking systemic hormone replacement therapy or endocrine treatment

Recruitment start date

03/10/2016

Recruitment end date

03/10/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Portsmouth Hospitals NHS Trust
Queen Alexandra Hospital Southwick Hill Road Cosham
Portsmouth
PO6 3LY
United Kingdom

Sponsor information

Organisation

Portsmouth Hospitals NHS Trust

Sponsor details

Queen Alexandra Hospital
Pathology Centre
Histopathology
Southwick Hill Road
Cosham
Portsmouth
PO6 3LY
United Kingdom
02392 286000 Ext. 3774
Juan.CamposPerez@porthosp.nhs.uk

Sponsor type

Hospital/treatment centre

Website

http://www.porthosp.nhs.uk/

Funders

Funder type

Charity

Funder name

League of Friends, Portsmouth Hospitals Charity

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The Investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and any other publications arising from the study. Authors will acknowledge the organisation that funded the study. Authorship will be determined in accordance with the ICMJE guidelines and other contributors will be acknowledged. Results of this study will be disseminated through publications in scientific journals, presentations at cancer research and scientific conferences, academic presentations and press releases.

Intention to publish date

15/06/2020

Participant level data

Stored in repository

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

16/01/2018: 16/10/2017: Internal review. 06/06/2017: Internal review 21/04/2017: The scientific title has been amended (originally "Early detection of women at high risk of developing endometrial cancer: a multivariate prediction model with the combination of lifestyle factors, clinical biochemistry, histological and genetic analysis"). In addition, the exclusion criteria have been updated and the study acronym has been added.