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Trials. 2017 Aug 29;18(1):394. doi: 10.1186/s13063-017-2085-2.

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.

Author information

1
Pelican Cancer Foundation, The Ark, Basingstoke, RG24 9NN, UK.
2
North Hampshire Hospital Foundation Trust, Basingstoke, RG24 9NA, UK.
3
Department of Medicine Royal Marsden Hospital Sutton, Sutton, SM2 5PT, UK.
4
Velindre Cancer Centre Velindre Hospital Cardiff, Cardiff, CF4 7XL, UK.
5
Gastrointestinal Unit Royal Marsden Hospital Sutton, Sutton, SM2 5PT, UK.
6
Department of Colorectal Surgery, Royal Marsden Hospital London, London, SW3 6JJ, UK.
7
Department of Surgery and Department for Tissue Microarray analysis, University of Southampton, Southampton, SO16 6YD, UK.
8
Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, Wellcome Trust Brenner Building, St. James's University Hospital, Leeds, LS9 7TF, UK.
9
Department of Pathology Radboud University, Nijmegen, 6500HB, Netherlands.
10
Division of Molecular Pathology Institute of Cancer Research, London, SW3 6JB, UK.
11
Statistics Unit, R&D Royal Marsden Hospital Sutton, Sutton, SM2 5PT, UK.
12
Department of Radiology, Royal Marsden Hospital Sutton, Sutton, SM2 5PT, UK.
13
Department of Radiology, Royal Marsden Hospital Sutton, Sutton, SM2 5PT, UK. gina.brown@rmh.nhs.uk.

Abstract

BACKGROUND:

Pre-operative chemoradiotherapy (CRT) for MRI-defined, locally advanced rectal cancer is primarily intended to reduce local recurrence rates by downstaging tumours, enabling an improved likelihood of curative resection. However, in a subset of patients complete tumour regression occurs implying that no viable tumour is present within the surgical specimen. This raises the possibility that surgery may have been avoided. It is also recognised that response to CRT is a key determinant of prognosis. Recent radiological advances enable this response to be assessed pre-operatively using the MRI tumour regression grade (mrTRG). Potentially, this allows modification of the baseline MRI-derived treatment strategy. Hence, in a 'good' mrTRG responder, with little or no evidence of tumour, surgery may be deferred. Conversely, a 'poor response' identifies an adverse prognostic group which may benefit from additional pre-operative therapy.

METHODS/DESIGN:

TRIGGER is a multicentre, open, interventional, randomised control feasibility study with an embedded phase III design. Patients with MRI-defined, locally advanced rectal adenocarcinoma deemed to require CRT will be eligible for recruitment. During CRT, patients will be randomised (1:2) between conventional management, according to baseline MRI, versus mrTRG-directed management. The primary endpoint of the feasibility phase is to assess the rate of patient recruitment and randomisation. Secondary endpoints include the rate of unit recruitment, acute drug toxicity, reproducibility of mrTRG reporting, surgical morbidity, pathological circumferential resection margin involvement, pathology regression grade, residual tumour cell density and surgical/specimen quality rates. The phase III trial will focus on long-term safety, regrowth rates, oncological survival analysis, quality of life and health economics analysis.

DISCUSSION:

The TRIGGER trial aims to determine whether patients with locally advanced rectal cancer can be recruited and subsequently randomised into a control trial that offers MRI-directed patient management according to radiological response to CRT (mrTRG). The feasibility study will inform a phase III trial design investigating stratified treatment of good and poor responders according to 3-year disease-free survival, colostomy-free survival as well as an increase in cases managed without a major resection.

TRIAL REGISTRATION:

ClinicalTrials.gov, ID: NCT02704520 . Registered on 5 February 2016.

KEYWORDS:

Chemoradiotherapy; Complete response; Randomised control trial; Rectal cancer; Tumour cell density; Tumour regression; mrTRG

PMID:
28851403
PMCID:
PMC5576102
DOI:
10.1186/s13063-017-2085-2
[Indexed for MEDLINE]
Free PMC Article

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