Magnetic Resonance Tumour Regression Grade (mrTRG) as a Novel Biomarker - Phase III Non CTIMP Trial
- Conditions
- Rectal Cancer
- Interventions
- Diagnostic Test: High resolution MRI scanDiagnostic Test: mrTRG assessment
- Registration Number
- NCT02704520
- Lead Sponsor
- Imperial College London
- Brief Summary
Open to patients undergoing any pre-operative treatment for locally advanced rectal cancer, TRIGGER is the only phase III clinical trial in the UK offering watch and wait. All patients will have post treatment MRI scans routinely performed, no change from the MERCURY trials high resolution MRI protocol is required. Patients will be randomised to either the control arm for management according to national guidelines - conventional MDT, clinical assessment post-treatment planning using the baseline MRI. Patients in the interventional arm will have their post treatment MRI scans read by a radiologist trained and supported to reliably report the mrTRG grade and have their management directed accordingly - 'Good response' (mrTRG 1\&2) - watch and wait (avoidance of surgery) offered. 'Poor response' (mrTRG 3-5) - local colorectal MDT is informed and uses information to discuss and agree next steps in treatment and surveillance. Patients are followed up for five years with QoL questionnaires completed at registration, 3 and 5 years.
- Detailed Description
The only phase III clinical trial in the UK offering watch and wait, the TRIGGER trial aims to validate mrTRG as an imaging biomarker for the stratified management of patients with locally advanced rectal cancer. The 'good responders' (mrTRG1\&2) often have no evidence of tumour and it may be possible to avoid surgery in this group and so maintaining QoL while not impacting survival rates. The 'poor responders' (mrTRG3-5) are at high risk of poor oncological outcomes and this knowledge is useful in planning ongoing treatment and surveillance.
TRIGGER is now a non-cTIMP trial as the protocol does not specify chemotherapy or IMP treatments. Decisions about the use of chemotherapy will be based upon local MDT discussions as is normal practice and national policy and the trial CRFs will capture these decisions and whether more treatment is given to patients or not. TRIGGER does not mandate or recommend the use of any treatments: specifically it does not suggest the use of investigational medicinal products. If any centre wishes to use IMPs this would be in the context of separate trial protocols and would not preclude entry into TRIGGER.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 441
- MRI defined locally advanced rectal carcinoma i.e. one or more: greater than or equal to mrT3c; mrEMVI positive; mr N1c; mr CRM positive
- Biopsy confirmed adenocarcinoma of radiologically defined rectum
- Be deemed to require preoperative chemoradiotherapy (CRT) or total neoadjuvant therapy (TNT)
- Metastatic disease
- MRI, radiotherapy and/or chemotherapy contraindications
- A post-treatment MRI performed more than 10 weeks after the completion of radiotherapy if given
- Previous malignancy within preceding 5 years if risk of recurrence >5%
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control arm High resolution MRI scan Management according to national guidelines - conventional MDT, clinical assessment post-treatment planning Intervention arm mrTRG assessment mrTRG directed management 'Good response' (mrTRG 1\&2) - deferral of surgery (watch \& wait) offered. 'Poor response' (mrTRG 3-5) - local colorectal MDT is informed and uses information to discuss and agree next steps in treatment and surveillance. Intervention arm High resolution MRI scan mrTRG directed management 'Good response' (mrTRG 1\&2) - deferral of surgery (watch \& wait) offered. 'Poor response' (mrTRG 3-5) - local colorectal MDT is informed and uses information to discuss and agree next steps in treatment and surveillance.
- Primary Outcome Measures
Name Time Method To show that patients can successfully avoid surgery after achieving a good response to treatment as measured on MRI (mrTRG). Up to 5 years Non-inferiority of overall survival at 3 years for the mrTRG (MRI Tumour Regression Grade) good response group (mrTRG 1 and 2) compared with control.
- Secondary Outcome Measures
Name Time Method Surgical morbidity 12 months post operative Comparison by arm of late (up to 12 months) surgical morbidity according to the Clavien-Dindo classification.
To investigate the effect of the preoperative treatment regime on mrTRG measurement Up to 2 years, 3 years and 5 years Reporting of treatment given against measurement of mrTRG (MRI Tumour Regression Grade) response (mrTRG 1 good to mrTRG 5 poor)
To describe the prognostic features associated with good and poor response to treatment as measured by MRI (mrTRG) 3 years and 5 years Correlation of baseline and post treatment prognostic factors on imaging and pathology against survival outcomes
To show mrTRG (Tumour Regression Grade) as a measurement tool can be reproduced by appropriately trained radiologists. Up to 2 years Agreement between local and centrally measured mrTRG (MRI Tumour Regression Grade) (mrTRG 1 good to mrTRG 5 poor)
To investigate the effect of the preoperative treatment regime on survival outcomes Up to 2 years, 3 years and 5 years Reporting of treatment given survival outcomes
To investigate the effect of mrTRG directed treatment strategy on Quality of Life 1 year, 2 years, 3 years and 5 years Quality of life assessed using EORTC QLQ-C30, EQ-5D and Low Anterior Resection Syndrome Score (LARS).scans performed at baseline, post-CRT and during surveillance schedule.
To assess whether the detection of ctDNA predicts for relapse in patients with locally advanced rectal cancer Up to 2 years, 3 years and 5 years Correlate ctDNA levels with outcome measures of mrTRG (MRI Tumour Regression Grade) (mrTRG 1 good to mrTRG 5 poor) and survival outcomes
To investigate the economic impact of introducing an mrTRG directed treatment strategy Up to 2 years, 3 years and 5 years Healthcare costs using NHS Reference Costs combined with health resource utilization and QoL data
To define molecular and immunological characteristics associated with treatment response as measured by MRI (mrTRG). Up to 2 years, 3 years and 5 years Correlate molecular and immunological biomarkers with outcome measures of mrTRG (MRI Tumour Regression Grade) response, (mrTRG 1 good to mrTRG 5 poor) and survival outcomes
Trial Locations
- Locations (10)
University Hospital of North Tees
🇬🇧Stockton-on-Tees, United Kingdom
Colchester General Hospital
🇬🇧Colchester, United Kingdom
NHS Lanarkshire - Hairmyres Hospital
🇬🇧East Kilbride, United Kingdom
Bristol Royal Infirmary
🇬🇧Bristol, United Kingdom
Diana Princess of Wales Hospital
🇬🇧Grimsby, United Kingdom
Royal Marsden NHS Foundation Trust
🇬🇧Sutton, United Kingdom
Aberdeen Royal Infirmary - NHS Grampion
🇬🇧Aberdeen, Aberdeenshire, United Kingdom
Hampshire Hospitals NHS Foundation Trust
🇬🇧Basingstoke, Hampshire, United Kingdom
University Hospital of North Midlands NHS Trust - Royal Stoke
🇬🇧Stoke-on-Trent, Staffordshire, United Kingdom
Salisbury NHS Foundation Trust
🇬🇧Salisbury, Wiltshire, United Kingdom