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

Table 4 Intervention arm – ‘good response’ to chemoradiotherapy

Intervention arm – good responders		Registration period	Intervention phase					Follow-up	Disease status^g
Visit type	Prior to patient entry	Registration	Randomisation (baseline)	Post CRT	MDT	No surgery	Chemotherapy for 24 weeks^f	Follow surveillance schedule for patients who defer surgery for a period of 5 years from end of chemotherapy (Table 3). If surgery is undertaken (patient declines deferral of surgery or regrowth is detected during follow-up) then the follow-up schedule for the control arm should be used. The Surgery and Surgical Morbidity CRFs should be completed as per control schedule. In the case of regrowth a Surveillance CRF should also be completed.	10 years
Timelines		≤4 weeks prior to CRT	During CRT	4–6 weeks post CRT	Review of restaging MRI including mrTRG reporting. mrTRG-directed management results in option of deferral of surgery (mrTRG I and II). The option of deferral of surgery is discussed with patient		≤12 weeks post CRT. Toxicity assessed at end of each cycle during chemotherapy		From end of CRT
Informed consent^a		X	X
Check eligibility criteria		X	X
Diagnosis and clinical assessment		X
Randomisation			X
Quality of life		X
Chemoradiotherapy			X
Blood sample^b		X		X
Baseline MRI	X
Restaging MRI^c				X			X
Pathology^d
Chemotherapy							X end of each cycle
Toxicity assessment							X end of each cycle
Annual follow-up									X
Adverse events^e				X			X end of each cycle
Concurrent medications		X	X	X			X end of each cycle

CRT pre-operative chemoradiotherapy, MDT multidisciplinary team, MRI magnetic resonance imaging, mrTRG MRI tumour regression grade
The X also denotes that Clinical Report Forms (CRFs) need completing
^aEligible subjects will be asked to provide written informed consent at registration and before randomisation
^bIf patient has consented to additional blood sample collection for research
^cThe post-CRT MRI should to be performed within 4–6 weeks (maximum of 10 weeks) from completion of CRT. A further MRI should be performed mid-way through chemotherapy treatment at approximately 12 weeks
^dResected specimen will be prepared and evaluated using a standardised protocol
^eAll adverse events will be recorded from the date the post-CRT MRI scan is performed until 30 days after the last dose of chemotherapy is administered during the intervention phase of the trial
^fInitial staging indicated these tumours were locally advanced; therefore, all patients are offered a systemic chemotherapy regimen equivalent to post-operative adjuvant chemotherapy. If regrowth occurs during chemotherapy patient should proceed to surgery and discuss the pathology at MDT to decide if remaining cycles should be given post-operatively
^gDisease status at 10 years (does not require clinic visit): alive without metastatic or recurrent disease, alive with metastatic and/or recurrent disease (date diagnosed), dead (date of death)

ISSN: 1745-6215