Longitudinal Sample Collection to Investigate Adaptation and Evolution of Ovarian High-grade Serous Carcinoma

Ovarian Cancer Clinical Trial

— BriTROC-2  

Official title:

Longitudinal Sample Collection to Investigate Adaptation and Evolution of Ovarian High-grade Serous Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05537844
• Other study ID #: BriTROC2-2019
• Status: Recruiting
• Start date: October 27, 2021
• Est. completion date: April 27, 2025

Study information

• Verified date: September 2022
• Source: Cancer Research UK, Glasgow
• Contact: Liz-Anne Lewsley
• Phone: 01413017193
• Email: liz-anne.lewsley[@]glasgow.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: April 27, 2025
• Est. primary completion date: October 27, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 16 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• BRCA1 Mutation
• BRCA2 Mutation
• Carcinoma
• Carcinosarcoma
• Carcinosarcoma, Ovarian
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• High Grade Serous Carcinoma
• Mixed Tumor, Mullerian
• Ovarian Cancer
• Primary Peritoneal Carcinoma

Locations

Country	Name	City	State
United Kingdom	Bristol Haematology & Oncology Centre	Bristol
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	The Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Hammersmith Hospital	London
United Kingdom	Royal Marsden Hospital NHS Trust	London
United Kingdom	St Bartholomew's Hospital	London
United Kingdom	University College London Hospital	London
United Kingdom	St Mary's Hospital	Manchester
United Kingdom	The Christie Hospital NHS Trust	Manchester
United Kingdom	Mount Vernon Cancer Centre	Northwood

Sponsors (2)

Lead Sponsor	Collaborator
Liz-Anne Lewsley	Ovarian Cancer Action

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumour Biopsies (to be collected from 250 patients)	To obtain tumour biopsies from 250 women with newly diagnosed high-grade carcinoma of the ovary, fallopian tube or peritoneum - all those with high-grade serous carcinoma (HGSC), high-grade endometrioid carcinoma or carcinosarcoma will be eligible.	Through study completion, an average of 1 year
Secondary	Whole Blood Samples for germline DNA isolation	To obtain whole blood for germline DNA isolation.	Baseline
Secondary	Plasma Blood Samples (to be collected for storage for future analyses)	To obtain plasma for ctDNA at diagnosis, during first line chemotherapy, at follow up and at the time of relapse.	Baseline and prior to Cycles 1-3 of chemotherapy (depending on treatment this could be up to 28 days), relapse
Secondary	Ascites/Peritoneal Washings (where possible from diagnosis and relapse)	To obtain ascites/washings from women at diagnosis and at the time of relapse.	Through study completion, an average of 1 year