Can cytology replace tumor tissue in determining somatic mutations of BRCA 1/2 genes in patients with epithelial carcinoma of ovaries, fallopian tubes or peritoneal serous carcinoma?

ISRCTN	ISRCTN42408038
DOI	https://doi.org/10.1186/ISRCTN42408038
Secondary identifying numbers	N/A

Submission date: 19/11/2015
Registration date: 24/11/2015
Last edited: 27/08/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
In patients with high grade serous epithelial cancer (i.e. involving cancer cells lining a cavity that contains fluid – such as the abdominal cavity - that look very abnormal and growing aggressively) of the ovaries, fallopian tubes or serous peritoneal (lining of the abdomen) cancer the risk of BRCA 1/2 gene mutations is up to 22%. Mutations of BRCA 1/2 genes can be either germline (inherited) or somatic (mutations caused by, for example, exposure to chemicals). Recently, a new targeted drug called olaparib has been approved for treatment of relapsed (cancer that, having gone into remission after treatment has come back) high-grade serous cancer of the ovaries, fallopian tubes or peritoneum in patients with known BRCA 1/2 gene mutations (either germline or somatic).
At the moment the testing for BRCA 1/2 gene mutations is provided from blood sample analysis (after prior genetic counselling) providing information about germline mutations only. For somatic mutations of BRCA 1/2 genes, samples of tumor tissue (paraffin-embeded samples) are recommended. However, it is known that paraffin causes difficulties in determining genetic mutations from tumor tissues. The aim of this study is to determine if cytology material (body cells) obtained from malignant ascites (fluid build-up resulting from cancer) provides the same quality of tumor DNA than material obtained from tumor tissue for detection of BRCA 1/2 somatic gene mutations in patients with high-grade serous epithelial carcinoma of ovaries, fallopian tubes or serous peritoneal carcinoma.

Who can participate?
Women with malignant ascites caused by high-grade serous epithelial carcinoma of the ovaries, fallopian tubes or serous peritoneal carcinoma (cancer of the lining of the abdomen).

What does the study involve?
Participants are asked to give blood, tumor tissue (paraffin-embeded) and ascites (fluid) samples. These samples are then analysed for BRCA 1/2 gene mutations. From ascites and tumor tissue information about somatic BRCA 1/2 gene mutations are provided, whereas from blood sample information about germline mutations of BRCA 1/2 gene mutations are provided.

What are the possible benefits and risks of participating?
None - no influence on standard treatment.

Where is the study run from?
Institute of Oncology Ljubljana (Slovenia)

When is the study starting and how long is it expected to run for?
From October 2015 to December 2017

Who is funding the study?
1. Institute of Oncology Ljubljana (Slovenia)
2. AstraZeneca UK

Who is the main contact?
Dr. Erik Škof

Contact information

Dr Erik Skof
Scientific

Department for Medical Oncology
Institute of Oncology Ljubljana
Zaloska 2
Ljubljana
1000
Slovenia

Study information

Study design	Single-centre diagnostic trial
Primary study design	Observational
Secondary study design	Cross sectional study
Study setting(s)	Hospital
Study type	Diagnostic
Scientific title	Can cytology replace tumor tissue in determining somatic mutations of BRCA 1/2 genes in patients with epithelial carcinoma of ovaries, fallopian tubes or peritoneal serous carcinoma? A single-centre diagnostic trial
Study objectives	Cytology material obtained from malignant ascites provides the same quality of tumor DNA than material obtained from tumor tissue for detection of BRCA 1/2 somatic gene mutations in patients with epithelial carcinoma of ovaries, fallopian tubes or serous peritoneal carcinoma
Ethics approval(s)	1. The Republic of Slovenia Commission for Medical Ethics (Komisija Republike Slovenije za Medicinsko Etiko), 27/ 07/ 2015, ref: KME 100/05/15 2. Republic of Slovenia National Medical Ethics Committee, 27/07/2015, ref: NMEC 100/05/15
Health condition(s) or problem(s) studied	Malignant ascites in patients with high grade serous cancer of ovaries, fallopian tubes or peritoneal serous cancer
Intervention	In each eligible patient, testing for somatic BRCA 1/2 gene mutations will be provided from malignant ascites and tumor tissue (paraffin block) and testing for germline BRCA 1/2 gene mutations from a blood sample.
Intervention type	Genetic
Primary outcome measure	Determination of somatic BRCA 1/2 gene mutations from cytology material provided from malignant ascites and tumor tissue - 100% correlation expected, proper method to be identified.
Secondary outcome measures	N/A
Overall study start date	01/02/2015
Completion date	31/12/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target number of participants	40
Key inclusion criteria	1. Malignant ascites determined by cytology 2. Histology proven high-grade serous cancer of ovaries, fallopian tubes or serous peritoneal cancer
Key exclusion criteria	1. Non-malignant ascites 2. Histology other than high-grade serous cancer of ovaries, fallopian tubes or serous peritoneal cancer
Date of first enrolment	01/10/2015
Date of final enrolment	31/12/2017

Locations

Countries of recruitment

Slovakia
Slovenia

Study participating centre

Institute Of Oncology Ljubljana

Zaloska 2
Ljubljana
1000
Slovenia

Sponsor information

Institute of Oncology Ljubljana
Hospital/treatment centre

Zaloska 2
Ljubljana
1000
Slovenia

Website	www.onko-i.si
"ROR"	https://ror.org/00y5zsg21

Funders

Funder type

Hospital/treatment centre

Institute Of Oncology Ljubljana (Slovenia)

No information available

AstraZeneca
Government organisation / For-profit companies (industry)

Alternative name(s): AstraZeneca PLC, Pearl Therapeutics
Location: United Kingdom

Results and Publications

Intention to publish date	01/06/2018
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
Publication and dissemination plan	Annual ASCO or ESMO meeting – preliminary results in 2017 Scientific paper with significant SCI after end of trial
IPD sharing plan	The data-sharing plans for the current study are unknown and will be made available at a later date

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	02/04/2019		Yes	No
Other publications		10/03/2022	03/01/2023	Yes	No
Results article		22/08/2024	27/08/2024	Yes	No

Editorial Notes

27/08/2024: Publication reference added.
03/01/2023: Publication reference added.
04/04/2019: Publication reference added.