Condition category
Cancer
Date applied
03/04/2013
Date assigned
27/08/2013
Last edited
04/09/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Ms Liz-Anne Lewsley

ORCID ID

Contact details

Beatson Oncology Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom
Liz-Anne.Lewsley@glasgow.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

13727

Study information

Scientific title

BriTROC1: Sample collection study to investigate the role of Homologous Recombination Deficiency in platinum sensitivity in recurrent high grade serous ovarian cancer

Acronym

BriTROC1

Study hypothesis

We hypothesise that the prevalence of patients with pre-existing Homologous Recombination Deficiency (HRD), including germline and somatic BRCA1 and BRCA2 mutation and epigenetic silencing, will be higher in platinum-sensitive relapsed populations than in platinum-resistant patients. Taken together with mutation analysis of other HRD genes, the overall proportion of HRD in platinum-sensitive relapsed high grade serous ovarian cancer (HGSOC) may be 50-60%.

Examination of HRD biomarkers in biopsy tissue at the time of relapse, together with comparison with original tissue and germline DNA, will identify markers of platinum response as well as novel mechanisms of resistance.

This is a multi-centre, non-randomised sample collection study in patients with recurrent high grade serous ovarian, primary peritoneal or fallopian tube cancer who have received prior platinum containing chemotherapy.

The primary objective is to demonstrate the safety and feasibility of acquiring tumour biopsies from women with relapsed ovarian cancer in multiple centres.

The primary endpoint is to obtain 300 fit-for purpose imaging-guided biopsies from women with relapsed ovarian cancer within three years.

More details can be found at: http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=13727

Ethics approval

NRES Committee East of England - Cambridge Central, 23 August 2012, ref: 12/EE/0349

Study design

Multi-centre centre non-randomised sample collection observational study

Primary study design

Observational

Secondary study design

Other

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

Patient information sheet is available on the Cancer Research UK Clinical Trials Unit website: http://www.cactusonline.org.uk/rep/open_in_house_trials_yd7r63sh.pdf

Condition

Topic: National Cancer Research Network; Subtopic: Gynaecological Cancer; Disease: Ovary/Fallopian tube

Intervention

Imaging guided (Ultrasound or CT), intra-operative or other suitable biopsies will be taken for research purposes from women who meet the eligibility criteria and who have been given written, informed consent. Blood will also be taken for storage of plasma and extraction of genomic DNA. Ascites will be collected if present and if drainage is deemed clinically indicated. For patients who consent, a further biopsy at subsequent relapse of disease will be taken. Patients will not be followed up within the context of this study.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

To obtain 300 fit-for purpose tumour biopsies from women with relapsed high grade serous ovarian cancer. Patients will have biopsy at baseline. This will take place at baseline after consent.

Secondary outcome measures

1. Assessment of mutations in HRD genes, BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, in relapsed HGSOC samples by targeted sequencing.
2. Comparison of allelic ratio of BRCA1 and BRCA2 in relapsed HGSOC and archival tumour samples taken at the time of diagnosis.
3. Analysis of mutations in TP53 (positive control for high grade serous pathology), PTEN, APC, BRAF, KRAS, PIK3CA in relapsed HGSOC and archival tumour samples.
4. Assessment of germline DNA mutations in BRCA1, BRCA2, RAD51C, RAD51D, BRIP1 in women with relapsed HGSOC.
5. Assessment of methylation of BRCA1 and BRCA2 in relapsed HGSOC and archival tumour samples taken at the time of diagnosis.

Timepoints: Baseline blood samples and pre chemotherapy (cycles 1 and 2, optional), archival tumour samples from original surgery.

Overall trial start date

11/12/2012

Overall trial end date

11/12/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients with recurrent histologically-proven high grade serous ovarian cancer, primary peritoneal carcinoma or fallopian tube cancer.
2. Patients may have received no more than two lines of prior chemotherapy
3. Availability of formalin-fixed, paraffin-embedded tissue taken at the time of original diagnosis of high grade serous ovarian cancer. This may be primary surgical debulking specimen OR core biopsy. For those with only a core biopsy from time of diagnosis, availability of specimen taken at interval debulking surgery is desirable, but not essential.
4. Patients must have disease deemed suitable for imaging-guided biopsy (ultrasound or CT) by an experienced radiologist.
5. Target Gender: Female, age ≥ 18 years
6. Written informed consent.
7. Able to apply with study procedures.
8. Life expectancy > 3 months
9. No contraindication to biopsy as appropriate

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

UK Sample Size: 300

Participant exclusion criteria

1. Ovarian, primary peritoneal or fallopian tube cancer of non-high grade serous pathology i.e. low grade serous, clear cell and endometrioid as well as carcinosarcoma/Malignant Mixed Mullerian Tumor (MMMT)
2. Borderline/low malignant potential tumours
3. Any non-epithelial ovarian malignancy
4. Patients with asymptomatic rising CA125 with no radiological evidence of recurrent ovarian cancer.
5. Original diagnosis of high grade serous cancer made on cytology only

Recruitment start date

11/12/2012

Recruitment end date

11/12/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Beatson Oncology Centre
Glasgow
G12 0YN
United Kingdom

Sponsor information

Organisation

NHS Greater Glasgow & Clyde (UK)

Sponsor details

Tennent Building
38 Church Street
Glasgow
G11 6NT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.nhsgg.org.uk/

Funders

Funder type

Charity

Funder name

Ovarian Cancer Action (UK)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes