Clinical trial NCT04597710: Precision Medicine for Liver Tumours With Quantitative Magnetic Resonance Imaging and Whole Genome Sequencing
Official title: Precision Medicine for Liver Tumours With Quantitative Magnetic Resonance Imaging and Whole Genome Sequencing
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Liver Cancer
Liver Metastasis Colon Cancer
Keywords: MRI
Surgery
Whole genome sequencing
Lead sponsor: Perspectum
Sponsor class: INDUSTRY
First posted: 2020-10-22
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief 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


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of patients for whom clinically-actionable data is provided by whole genome sequencing at the time of surgery.
timeFrame: 36 months
Secondary outcomes:
measure: Proportion of patients for whom clinically-actionable data is provided by LiverMultiScan.
timeFrame: 36 months
measure: 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.
timeFrame: 36 months
measure: Correlation of MR measurements of steatosis and fibroinflammation with digital pathology and human pathology.
timeFrame: 36 months
measure: Performance of WGS and LiverMultiScan for predicting post-surgery length of stay in hospital, post-operative liver function, 1-year mortality and recurrence rates.
timeFrame: 36 months
measure: Proportion of patients for whom actionable biomarkers of drug sensitivity are identified with WGS.
timeFrame: 36 months
Other outcomes:
Locations:
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire Hospital
state: Hampshire
Study officials:
affiliation: Perspectum Ltd
name: Rajarshi Banerjee
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.