Colorectal cancer Cancer Malignant neoplasms of digestive organs
Conditions
Interventions
APHRODITE is a phase II, multi-centre, open-label, randomised-controlled trial of high dose radiotherapy versus standard dose radiotherapy for early rectal cancer. The primary aim is to assess whether
Sponsors
University of Leeds
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Biopsy confirmed adenocarcinoma of the rectum 2. Age 18 or over 3. Able to provide written informed consent 4. MDT deems patient unsuitable for radical TME surgical resection of their tumour either because they are considered to be at increased surgical risk from TME (for example due to 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 they have marked anxiety at the prospect of a stoma, or because of anticipated difficulty managing a stoma post-operatively (including physical causes such as arthritis, Dupuytren’s contracture and visual problems). 5. Patient is suitable for either pelvic radiotherapy or chemoradiation in the opinion of the treating oncologist 6. ECOG PS 0-2 7. Primary tumour is 1 mm from disease to levator ani or mesorectal fascia) 12.2 or threatened ( = 50 mls/min (estimated using a validated creatinine clearance calculation e.g. Cockroft and Gault, or Wright formula) 14. Absolute neutrophil count > 1.5 x 109/l; platelets > 100 x 109/l 15. Serum transaminase concentration < 3 x Upper Limit Normal (ULN) 16. Bilirubin concentration < 1.5 x ULN
Exclusion criteria
Exclusion criteria: 1. Nodal involvement identified by nodes showing irregular margins and or heterogeneous signal on the high resolution MRI (i.e. N1-N2) 2. The presence of EMVI discontinuous with the primary tumour 3. Discontinuous tumour deposits (N1c) 4. Dominant mucinous tumour on MRI 5. Signet ring carcinoma or tumours histopathologically containing a neuroendocrine component 6. Tumour has grown through and breached mesorectal fascia 7. Tumour involves or breaches the levator ani (as this would be T4b disease) 8. 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) 9. Undergone an attempt at complete local resection of their cancer 10. Previous pelvic radiotherapy 11. Definite distant metastases (equivocal distant metastases on the CT scan are permitted, e.g. indeterminate lung modules, sub-centimetre retroperitoneal nodes or indeterminate liver lesion) 12. Defunctioning colostomy or ileostomy has been fashioned 13. Prior invasive malignancy unless disease free for a minimum of 3 years (excluding basal cell carcinoma of the skin or other in situ carcinomas) 14. Prior systemic chemotherapy for colorectal cancer 15. Women who are pregnant, breastfeeding or a women of child bearing potential who are unwilling to use effective contraceptive methods
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Clinical complete response at 6 months from start of (chemo-)radiotherapy. Response to treatment will be assessed via clinical examination, endoscopy and imaging using pelvic MRI in accordance with the Tumour Regression Grading (mrTRG) system. Clinical complete response (cCR) will be defined as: 1. No evidence of either mucosal tumour or submucosal swelling on white light endoscopy. A flat white scar remains, with or without telangiectasia 2. No palpable tumour upon digital rectal examination (DRE) 3. High-resolution pelvic MRI scanning shows either a linear scar only, or dense fibrosis with no obvious tumour signal (mrTRG 1 or 2). Every effort should be made to ensure that trimodality assessment of response occurs at 3 and 6 months (endoscopy, DRE, MRI). However, in the unusual circumstance when this might not be possible for a specific patient, confirmation of a cCR should always include rectal endoscopy. If one of either DRE or MRI cannot be assessed for a specific patient, then confirmation of cCR may still occur based on the endoscopy plus either DRE (if tumour was originally palpable pre-treatment), or pelvic MRI | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Acute toxicity and late toxicity recorded during each visit using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). These time points will be at baseline, on treatment weeks 1,2,3,4,5,5.5, 7.5 and during follow up at the 3, 6, 9, 12 and 24 month visits. 2. Patient-reported outcome measures (PROMs) including health-related quality of life (HRQoL) will be collected after at baseline, at end of treatment at week 5.5, then during follow up at 3, 6, 9, 12 and 24 months. 3. Other information will be collected during visits, such as stoma rate, treatment compliance and overall survival but these will be collected if and when they occur. | — |
Countries
England, United Kingdom, Wales
Outcome results
None listed