Precision Medicine for Liver Tumours With Quantitative Magnetic Resonance Imaging and Whole Genome Sequencing (Precision1)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Liver Cancer; Liver Metastasis Colon Cancer
• Intervention / Treatment: Genetic: utility of whole genome sequencing (WGS) to aid clinical decision making in patients referred for liver resection

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• United Kingdom
  • Hampshire
    • Basingstoke, Hampshire, United Kingdom, RG249NA
      • Basingstoke And North Hampshire Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

The primary endpoint of the study is an evaluation of the number of patients for whom clinically actionable data is provided by whole genome sequencing.

Based on the following information, we will aim to recruit 200 patients from HHFT and expect to observe at least a 25% change in intended clinical management (at 95% confidence interval).

• A recent study using whole-genome analyses of metastatic solid tumours identified 31% of patients who present with a biomarker that predicts sensitivity to a drug and lacked any known resistance biomarkers for the same drug.
• The primary end-point can be achieved with only the first study visit, and so no drop-out is expected.

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Perspectum
• Investigators: Principal Investigator: Rajarshi Banerjee, Perspectum Ltd

Publications and helpful links

General Publications

• Welsh FK, Connell JJ, Kelly M, Gooding S, Banerjee R, Rees M. Precision medicine for liver tumours with quantitative MRI and whole genome sequencing (Precision1 trial): study protocol for observational cohort study. BMJ Open. 2022 Apr 5;12(4):e057163. doi: 10.1136/bmjopen-2021-057163.

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2021
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: October 13, 2020
• First Submitted That Met QC Criteria: October 15, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): August 24, 2023
• Last Update Submitted That Met QC Criteria: August 23, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: MRI; Surgery; Whole genome sequencing
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms
• Other Study ID Numbers: 20/PR/0222

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No