Clinical trial NCT02704520: Magnetic Resonance Tumour Regression Grade (mrTRG) as a Novel Biomarker - Phase III Non CTIMP Trial
Official title: Magnetic Resonance Tumour Regression Grade (mrTRG) as a Novel Biomarker to Stratify Management of Good and Poor Responders to Radiotherapy: A Rectal Cancer Multicentre Randomised Control Trial to Avoid Surgery With 'Watch and Wait' or Intensify Treatment According to mrTRG
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Rectal Cancer
Keywords: Rectal Cancer
Magnetic Resonance Imaging
Chemoradiotherapy
Chemotherapy
Diagnostic Imaging
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2016-03-10
Enrollment: 441
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. MRI defined locally advanced rectal carcinoma i.e. one or more: greater than or equal to mrT3c; mrEMVI positive; mr N1c; mr CRM positive
2. Biopsy confirmed adenocarcinoma of radiologically defined rectum
3. Be deemed to require preoperative chemoradiotherapy (CRT) or total neoadjuvant therapy (TNT)

Exclusion Criteria:

1. Metastatic disease
2. MRI, radiotherapy and/or chemotherapy contraindications
3. A post-treatment MRI performed more than 10 weeks after the completion of radiotherapy if given
4. Previous malignancy within preceding 5 years if risk of recurrence \>5%

Primary outcomes:
measure: To show that patients can successfully avoid surgery after achieving a good response to treatment as measured on MRI (mrTRG).
timeFrame: Up to 5 years
Secondary outcomes:
measure: To describe the prognostic features associated with good and poor response to treatment as measured by MRI (mrTRG)
timeFrame: 3 years and 5 years
measure: To show mrTRG (Tumour Regression Grade) as a measurement tool can be reproduced by appropriately trained radiologists.
timeFrame: Up to 2 years
measure: Surgical morbidity
timeFrame: 30 days post operative
measure: Surgical morbidity
timeFrame: 12 months post operative
measure: To investigate the effect of the preoperative treatment regime on mrTRG measurement
timeFrame: Up to 2 years, 3 years and 5 years
measure: To investigate the effect of the preoperative treatment regime on survival outcomes
timeFrame: Up to 2 years, 3 years and 5 years
measure: To investigate the effect of mrTRG directed treatment strategy on Quality of Life
timeFrame: 1 year, 2 years, 3 years and 5 years
measure: To investigate the economic impact of introducing an mrTRG directed treatment strategy
timeFrame: Up to 2 years, 3 years and 5 years
measure: To define molecular and immunological characteristics associated with treatment response as measured by MRI (mrTRG).
timeFrame: Up to 2 years, 3 years and 5 years
measure: To assess whether the detection of ctDNA predicts for relapse in patients with locally advanced rectal cancer
timeFrame: Up to 2 years, 3 years and 5 years
Other outcomes:
Locations:
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary - NHS Grampion
state: Aberdeenshire
city: Basingstoke
country: United Kingdom
facility: Hampshire Hospitals NHS Foundation Trust
state: Hampshire
city: Stoke-on-Trent
country: United Kingdom
facility: University Hospital of North Midlands NHS Trust - Royal Stoke
state: Staffordshire
city: Salisbury
country: United Kingdom
facility: Salisbury NHS Foundation Trust
state: Wiltshire
city: Bristol
country: United Kingdom
facility: Bristol Royal Infirmary
city: Colchester
country: United Kingdom
facility: Colchester General Hospital
city: East Kilbride
country: United Kingdom
facility: NHS Lanarkshire - Hairmyres Hospital
city: Grimsby
country: United Kingdom
facility: Diana Princess of Wales Hospital
city: Stockton-on-Tees
country: United Kingdom
facility: University Hospital of North Tees
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Imperial College London
name: Gina Brown, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Battersby NJ, Dattani M, Rao S, Cunningham D, Tait D, Adams R, Moran BJ, Khakoo S, Tekkis P, Rasheed S, Mirnezami A, Quirke P, West NP, Nagtegaal I, Chong I, Sadanandam A, Valeri N, Thomas K, Frost M, Brown G. A rectal cancer feasibility study with an embedded phase III trial design assessing magnetic resonance tumour regression grade (mrTRG) as a novel biomarker to stratify management by good and poor response to chemoradiotherapy (TRIGGER): study protocol for a randomised controlled trial. Trials. 2017 Aug 29;18(1):394. doi: 10.1186/s13063-017-2085-2.