Status: Open
Specialty: Colorectal
Date Opened: 04/03/2020
Planned Close Date: 30/05/2025
Sponsor: CTRU - University of Leeds
Principal Investigator: Dr Deborah Williamson
Study Title: A Phase II trial of Higher RadiOtherapy Dose In The Eradication of early rectal cancer.
An increasing number of patients with early rectal cancer in the UK are being identified through the bowel screening programme. There is a growing number of patients who may not be suitable for surgery, due to other medical comorbidities and factors. These patients may suffer from symptoms as their cancer grows, including pain, diarrhoea and the need for a stoma (bowel bag). For these patients, radiotherapy combined with chemotherapy, or radiotherapy only is used. A standard dose of radiotherapy given over 5.5 weeks can lead to the cancer disappearing in about one third of patients. In this trial we want to find out if a higher radiotherapy dose given over the same time will give greater benefit to patients with acceptable side effects. This could lead to better treatment and improved quality of life.
Biopsy confirmed adenocarcinoma of the rectum
Age 18 or over
Able to provide written informed consent
Non-surgical management is deemed appropriate due to one of the following three reasons:
· Unsuitable for radical TME surgery, due to increased surgical risk from TME (for example due general frailty or due to specific co-morbidities which make anaesthetic or surgery hazardous, such as cardiac disease, pulmonary disease, renal failure, previous anaesthetic problems or previous pelvic surgery), OR
· Anticipated difficulty managing a stoma post-operatively (including physical causes such as arthritis, Dupuytren’s contracture and visual problems).
· Suitable for radical TME surgery in terms of performance status and general medical condition, but where the patient strongly prefers an attempt at organ preservation, aiming to try and avoid TME surgery.
Patient is suitable for either pelvic radiotherapy or chemoradiation in the opinion of the treating oncologist
ECOG PS 0-2
Primary tumour is visible on MRI
Primary tumour is ≤ 5 cm in maximum diameter
Primary tumour is staged at T1-T3b. (TNM staging as per UICC 8th Edition (Appendix B), with additional T3 subdivisions)
Superior aspect of tumour is at or below a horizontal line drawn from the anterior aspect of the S2/3 junction on pre-treatment MRI
Nodal disease is staged at N0-N1b i.e. a maximum of three involved mesorectal lymph nodes is permitted. Involved lymph nodes are defined morphologically i.e. demonstrating irregular margins and or heterogeneous signal on high resolution MRI.
· Nx nodal disease is also permitted i.e. nodes are equivocal for involvement.
· Superior aspect of involved lymph nodes is at or below a horizontal line drawn from the anterior aspect of the S2/3 junction on pre-treatment MRI
Mesorectal fascia or levator ani are clear (>1 mm from primary tumour or contiguous EMVI or nodal disease to mesorectal fascia or levator ani)
For patients intended to receive radiotherapy alone, or concurrent 5-Fluorouracil, there is no required level of renal function. Patients intended to receive capecitabine require an estimated creatinine clearance ≥ 30 ml/min (estimated using a validated creatinine clearance calculation e.g. Cockroft and Gault (Appendix D) or Wright formula)
· Absolute neutrophil count > 1.5 x 109/l; platelets > 100 x 109/l
· Serum transaminase concentration < 3 x Upper Limit Normal (ULN)
Bilirubin concentration < 1.5 x ULN
N2 disease; i.e. 4 or more involved mesorectal lymph nodes
Presence of discontinuous tumour deposits / discontiguous EMVI (N1c)
Dominant mucinous tumour on MRI
Signet ring carcinoma or tumours histopathologically containing a neuroendocrine component
Tumour threatens (≤ 1mm), involves or breaches the mesorectal fascia or levator ani
Involvement of anal intersphincteric plane or external anal sphincter or adjacent organs (If the participant has a low rectal tumour extending inferior to the puborectalis sling, involvement of the internal anal sphincter is permitted)
Undergone an attempt at complete local resection of their cancer
Previous pelvic radiotherapy
Definite distant metastases (equivocal distant metastases on the CT scan are permitted, e.g. indeterminate lung nodules, sub-centimetre retroperitoneal nodes or indeterminate liver lesions)
Defunctioning colostomy or ileostomy has been fashioned
Prior invasive malignancy unless disease free for a minimum of 3 years (excluding basal cell carcinoma of the skin or other in situ carcinomas)
Prior systemic chemotherapy for colorectal cancer
Women who are pregnant, breastfeeding or a women of child bearing potential who are unwilling to use effective contraceptive methods
Research Nurse: Rashmi Madan (x4656) Rashmi.Madan@LTHTR.nhs.uk
Administrator: Yecora Lecanda-Swarbrick (x3766)
Link to EDGE