Precision Medicine for Liver Tumours With Quantitative Magnetic Resonance Imaging and Whole Genome Sequencing

Liver Cancer Clinical Trial

— Precision1  

Official title:

Precision Medicine for Liver Tumours With Quantitative Magnetic Resonance Imaging and Whole Genome Sequencing

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04597710
• Other study ID #: 20/PR/0222
• Status: Active, not recruiting
• Start date: February 18, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: August 2023
• Source: Perspectum
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This will be a prospective, observational, cohort study to determine the impact of integrated diagnostics using quantitative magnetic resonance imaging, whole genome sequencing and digital pathology on intended patient management for liver cancer patients referred for liver resection. Participants with primary or secondary liver cancer will be recruited from Hampshire Hospitals NHS Foundation Trust in Basingstoke or Oxford University Hospitals NHSFoundation Trust in Oxford. The incidence of treatable liver tumours is on the rise globally, driven by obesity, viral hepatitis and metastases from colorectal cancers. Survival rates can be improved with optimised allocation of treatment options including surgical resection, radiofrequency ablation, embolisation, chemotherapy and targeted molecular therapies (including immunotherapy). The key motivation of this study is to help patients access the most suitable treatment combinations, based on integrating clinical, radiological and genomic data. A similar integrated approach, integrating radiology and pathology, has been shown to improve outcomes in breast cancer care. Detailed pathologic analysis of the surgical specimen from breast carcinoma biopsy provides valuable feedback to the radiologist, establishes the completeness of surgical intervention, and generates predictive information for therapeutic decisions. Whole genome sequencing (WGS) has discovered cancer driver mutations and the complex molecular profile of liver cancer. In many metastatic solid tumours, WGS has been used to identify a significant patient population (31%) who present with a biomarker that predicts sensitivity to a drug and lacked any known resistance biomarkers for the same drug. Identifying which patients possess druggable mutations will allow clinicians to make the optimal treatment decisions. The next challenge is integrating WGS into scalable clinical practice

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female 18 years of age and older willing and able to give informed consent to participate in the study
• Patients being considered for liver resection for primary or secondary liver cancer.

Exclusion Criteria:

• The participant may not enter the study with any known contraindication to magnetic resonance imaging (including but not limited to pregnancy, a pacemaker or other metallic unfixed implanted device, metallic fragments, extensive tattoos, severe claustrophobia).
• Any other cause, including a significant underlying disease or disorder which, in the opinion of the investigator, may put the participant at risk by participating in the study or limit the participant's ability to participate.

Related Conditions & MeSH terms

• Liver Cancer
• Liver Metastasis Colon Cancer
• Liver Neoplasms

Intervention

Genetic:
• utility of whole genome sequencing (WGS) to aid clinical decision making in patients referred for liver resection
All participants will attend their planned outpatient surgery appointment.The consultant will document the intended treatment plan for each participant in line with their usual care pathway.Following this, participants will be required to attend three dedicated study visits:The results of the MRI scans from Study Visit 1 will be analysed into a LiverMultiScan report.A report will be sent to the consultant who will review their original documented care plan alongside the LiverMultiScan report.The consultant may update the intended care plan as a result of the LiverMultiScan report, in line with the device CE-marking.Any changes to the care plan will be documented.The patient will then undergo their planned treatment.The tumour explant will be collected and samples will be stored, transported and processed for genetic sequencing and digital histopathology.Study Visit 2 will be performed remotely 12 months following their planned treatment,where patient reported outcomes will be collected

Locations

Country	Name	City	State
United Kingdom	Basingstoke and North Hampshire Hospital	Basingstoke	Hampshire

Sponsors (1)

Lead Sponsor	Collaborator
Perspectum

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients for whom clinically-actionable data is provided by whole genome sequencing at the time of surgery.	This will be evaluated retrospectively, with clinically-actionable data defined as data which would result in a clinician choosing a different medical intervention to the current standard of care.	36 months
Secondary	Proportion of patients for whom clinically-actionable data is provided by LiverMultiScan.	. To determine the utility of quantitative multiparametric MRI with LiverMultiScan to aid clinical decision making in patients referred for liver resection.	36 months
Secondary	Correlation of computationally-derived digital pathology results with human pathologist assessments of the tumour and non-tumour tissue, along with assessment of intra- and inter-rater variability.	To compare computationally-derived digital pathology results with human pathologist assessments of the tumour and non-tumour tissue.	36 months
Secondary	Correlation of MR measurements of steatosis and fibroinflammation with digital pathology and human pathology.	To compare histopathological assessments of liver fat and fibroinflammation with quantitative MRI metrics (cT1, PDFF)	36 months
Secondary	Performance of WGS and LiverMultiScan for predicting post-surgery length of stay in hospital, post-operative liver function, 1-year mortality and recurrence rates.	To evaluate the long term outcomes and recurrence rates and recurrence patterns of patients as it relates to imaging and whole genome sequencing.	36 months
Secondary	Proportion of patients for whom actionable biomarkers of drug sensitivity are identified with WGS.	To evaluate whether whole genome sequencing enables better stratification of patients prior to surgery.	36 months