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
+44 141 301 7193
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
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.
Ethics approval
NRES Committee East of England - Cambridge Central, 23/08/2012, ref: 12/EE/0349
Study design
Multi-centre centre non-randomised sample collection observational study
Primary study design
Observational
Secondary study design
Cohort study
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 measure
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
30/08/2018
Reason abandoned (if study stopped)
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
30/08/2017
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Beatson West of Scotland Cancer Centre
1053 Great Western Road
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
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 organizations
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
Basic results (scientific)
Publication list