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

• ClinicalTrials.gov Identifier: NCT04597710
• Recruitment Status: Active, not recruiting
• First Posted: October 22, 2020
• Last Update Posted: November 2, 2022
• Sponsor: Perspectum
• Information provided by (Responsible Party): Perspectum

Tracking Information

• First Submitted Date: October 13, 2020
• First Posted Date: October 22, 2020
• Last Update Posted Date: November 2, 2022
• Actual Study Start Date: February 18, 2021
• Estimated Primary Completion Date: August 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 15, 2020)

Proportion of patients for whom clinically-actionable data is provided by whole genome sequencing at the time of surgery. [ Time Frame: 36 months ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 15, 2020)

• Proportion of patients for whom clinically-actionable data is provided by LiverMultiScan. [ Time Frame: 36 months ]
  . To determine the utility of quantitative multiparametric MRI with LiverMultiScan to aid clinical decision making in patients referred for liver resection.
• 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. [ Time Frame: 36 months ]
  To compare computationally-derived digital pathology results with human pathologist assessments of the tumour and non-tumour tissue.
• Correlation of MR measurements of steatosis and fibroinflammation with digital pathology and human pathology. [ Time Frame: 36 months ]
  To compare histopathological assessments of liver fat and fibroinflammation with quantitative MRI metrics (cT1, PDFF)
• Performance of WGS and LiverMultiScan for predicting post-surgery length of stay in hospital, post-operative liver function, 1-year mortality and recurrence rates. [ Time Frame: 36 months ]
  To evaluate the long term outcomes and recurrence rates and recurrence patterns of patients as it relates to imaging and whole genome sequencing.
• Proportion of patients for whom actionable biomarkers of drug sensitivity are identified with WGS. [ Time Frame: 36 months ]
  To evaluate whether whole genome sequencing enables better stratification of patients prior to surgery.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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

• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Retention of histopathlogy samples: tumour and normal tissue; also serum, plasma and buffy coat, extracted DNA

• 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.

Condition

• Liver Cancer
• Liver Metastasis Colon Cancer

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

• Study Groups/Cohorts: Not Provided
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: October 15, 2020): 200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 1, 2023
• Estimated Primary Completion Date: August 1, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Not Provided
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT04597710
• Other Study ID Numbers: 20/PR/0222
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Perspectum
• Original Responsible Party: Same as current
• Current Study Sponsor: Perspectum
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Rajarshi Banerjee; Perspectum Ltd

• PRS Account: Perspectum
• Verification Date: November 2022