Clinical trial NCT05537844: Longitudinal Sample Collection to Investigate Adaptation and Evolution of Ovarian High-grade Serous Carcinoma
Official title: Longitudinal Sample Collection to Investigate Adaptation and Evolution of Ovarian High-grade Serous Carcinoma
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Ovarian Cancer
High Grade Serous Carcinoma
Carcinosarcoma, Ovarian
Fallopian Tube Cancer
Primary Peritoneal Carcinoma
BRCA1 Mutation
BRCA2 Mutation
Lead sponsor: Cancer Research UK, Glasgow
Sponsor class: OTHER
Collaborators: name: Ovarian Cancer Action
First posted: 2022-09-13
Enrollment: 250
Sex: FEMALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: In BriTROC-2, a cohort of women with presumed newly-diagnosed high-grade carcinoma of the ovary, fallopian tube or peritoneum will be recruited at the time of diagnosis and approached for consent to Part 1 (screening consent) of BriTROC-2. Up to 250 women with a confirmed diagnosis of high-grade serous/high-grade endometrioid or carcinosarcoma will be eligible for full consent (Part 2) and registration to BriTROC-2 and will be followed prospectively until first relapse. The aim of this study is to acquire tumour material at diagnosis and relapse, whole blood for genomic analysis and plasma for ctDNA. This study will also isolate single cells and establish organoid cultures from ascites/peritoneal washings.

Brief summary: In BriTROC-2, up to 250 women with a confirmed diagnosis of high-grade serous/high-grade endometrioid or carcinosarcoma will be eligible for full consent (Part 2) and registration to BriTROC-2 and will be followed prospectively until first relapse. Women with presumed newly-diagnosed high-grade serous carcinoma of the ovary, fallopian tube or peritoneum can be approached for consent to Part 1 (screening consent) of BriTROC-2 prior to formal diagnosis.

The aim of this study is to acquire tumour material at diagnosis and relapse, whole blood for genomic analysis and plasma for ctDNA. This study will also isolate single cells and establish organoid cultures from ascites/peritoneal washings.

Detailed description: BriTROC-2 is a sample collection study from women with ovarian cancer from the point of diagnosis to the time of disease relapse.

Ovarian cancer has a poor prognosis. The large majority of patients with ovarian cancer will relapse and ultimately develop fatal chemotherapy resistance. Although there is a wealth of information regarding the molecular basis of ovarian cancer at diagnosis, very little is known about the drivers of treatment resistance (both intrinsic and acquired) and the processes that are active at relapse. This research requires sequential collection of tumour material for women throughout the course of their disease.

This multicentre study will collect tumour samples, ascites (fluid within the abdomen) and blood from women with newly diagnosed ovarian cancer and follow these women through to relapse of their disease. The samples collected will be used to look at patterns within the tumour to identify those that are able to predict response to chemotherapy and outcome. Assays and models will be developed that can look at the process that are active in a tumour at time of sample acquisition. This will give clues into the mechanisms that drive treatment resistance. Ultimately this research aims to guide future treatment options for women with ovarian cancer.

Recruitment will be over 3 years and this study will be conducted at sites with expertise in managing ovarian cancer and the ability to carry out the appropriate sample collection and collect high quality clinical data.

This study is the second collaborative project within the UK to collect samples from women with ovarian cancer. The success of the first study, BriTROC-1, demonstrated the feasibility of sample collection from women with relapsed ovarian cancer. The methods and frameworks established in BriTROC-1 will be used for BriTROC-2.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 16 years.
2. Ability to provide written informed consent prior to participating in the trial and any trial related procedures being performed.
3. Ovarian, fallopian tube or primary peritoneal carcinoma of high-grade serous, high-grade (grade 3) endometrioid or carcinosarcoma histologies.
4. Patients with ovarian, fallopian tube or primary peritoneal carcinoma of any histological subtype in patients with known germline mutations in BRCA1 or BRCA2.
5. Willingness to comply with scheduled visits, treatment plans, laboratory tests and other trial procedures.
6. Life expectancy \> 6 months.
7. No contraindication to obtaining a surgical or image-guided biopsy.
8. Patients with confirmed ovarian, fallopian tube or primary peritoneal carcinoma of high-grade serous, high-grade (grade 3) endometrioid or carcinosarcoma histologies who have consented for their tissue to be collected under a generic tissue consent (i.e. have not consented to Part 1) may be eligible for full consent following discussion with the trials team.

Exclusion Criteria:

1. Ovarian, primary peritoneal or fallopian tube cancer of low grade serous, grades 1 or 2 endometrioid or clear cell subtypes unless associated with known germline mutation in BRCA1 or BRCA2
2. Borderline/low malignant potential tumours
3. Any non-epithelial ovarian malignancy
4. Diagnosis of high-grade serous cancer made on cytology only
5. Patients who have received any prior treatment for known high-grade ovarian carcinoma
6. Other severe or uncontrolled systemic disease or evidence of any other significant disorder or lab finding that makes it undesirable for the patient to participate in the trial
7. History of physical or psychiatric disorder that would prevent informed consent and compliance with protocol
8. Pregnant or lactating women
9. Patients with any other severe concurrent disease which may increase the risk associated with trial participation
10. Any psychological, familial, sociological or geographical consideration potentially hampering compliance with the trial protocol and follow up schedule.

Primary outcomes:
measure: Tumour Biopsies (to be collected from 250 patients)
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: Whole Blood Samples for germline DNA isolation
timeFrame: Baseline
measure: Plasma Blood Samples (to be collected for storage for future analyses)
timeFrame: Baseline and prior to Cycles 1-3 of chemotherapy (depending on treatment this could be up to 28 days), relapse
measure: Ascites/Peritoneal Washings (where possible from diagnosis and relapse)
timeFrame: Through study completion, an average of 1 year
Other outcomes:
Locations:
city: Bristol
country: United Kingdom
facility: Bristol Haematology & Oncology Centre
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital NHS Trust
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Manchester
country: United Kingdom
facility: St Mary's Hospital
city: Manchester
country: United Kingdom
facility: The Christie Hospital NHS Trust
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre
Study officials:
affiliation: Imperial College London
name: Iain McNeish
role: PRINCIPAL_INVESTIGATOR
References: