Can the Rectum be Saved by Watchful Waiting or TransAnal Surgery Following (Chemo)Radiotherapy Versus Total Mesorectal Excision for Early REctal Cancer?

• Status: Unknown status
• Trial end date: 2021-10-01
• Target enrollment: 0
• Participant gender: All

Summary

Colorectal cancer is the third most common tumour in the UK, Netherlands and Denmark with 41000, 14000 and 4000 new cases per year respectively. Standard primary radical Total Mesorectal Excision (TME) surgery is an oncologically effective treatment for early stage rectal cancer. However, resection of a low rectal tumour requires a permanent stoma in approximately 5-10% of cases while many more patients have a temporary stoma, some of which are not reversed. Radical surgery, which evolved to treat locally advanced, symptomatic tumours, may not be the optimal method of treatment for early screen-detected tumours and an organ preserving strategy may generate significantly less morbidity without substantially compromising oncological outcomes.

TREC was a randomised phase II trial to test the feasibility of randomisation between TME and an organ preserving policy of short course pre-operative radiotherapy (SCPRT) delay followed by transanal endoscopic microsurgery (TEM). STAR-TREC is a phase II feasibility study that will evaluate whether it is possible to accelerate the patient recruitment attained in the TREC study, to 4 per month in the first year of recruitment and 6 per month in the second. This would demonstrate deliverability of a phase III study.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Birmingham

Criteria

Inclusion Criteria:

• Biopsy proven adenocarcinoma of the rectum

• mriT1-3bN0 (with ≤5mm of mesorectal invasion) rectal tumour or endorectal ultrasound defined rectal cancer uT1-uT3b (optional: in centres where high quality ERUS is available and patient unable to tolerate MRI)

• MDT determines that all of the following treatment options are feasible:

• TME surgery

• CRT

• SCPRT

• TEM Patients with equivocal radiological lesions e.g. mesorectal, retroperitoneal, liver, lung are eligible if agreed by MDT

• Aged 16 or over in UK (18 or over in the Netherlands and Denmark).

• Pre-(chemo)radiotherapy treatment, the following criteria must be met :

• Estimated creatinine clearance >50 mls/min -Absolute neutrophil count >1.5x109/l; platelets >100 x 109/L-

• Serum transaminase <3 x Upper Limit Normal/l (ULN)

• Bilirubin <1.5 x ULN

• ECOG performance status 0-1

• If female and of childbearing potential, must:

• Have a negative pregnancy test ≤72hours prior to initiating study treatment

• Agree to avoid pregnancy during and for 6 months after study treatment

• If male with a partner of childbearing potential, must:

• Agree to use adequate, medically approved, contraceptive precautions during and for 90 days after the last dose of study treatment

• Patient able and willing to provide written informed consent for the study

Exclusion Criteria:

• Unequivocal evidence of metastatic disease (includes resectable metastases) as determined by

• MRI showing:

• node positive

• extramural vascular invasion (mriEMVI) positive

• defined mucinous tumour

• Maximum tumour diameter > 40mm as measured from everted edges (sagittal)

• Mesorectal fascia threatened (< 1 mm on MRI)

• Tumour position anterior, above the peritoneal reflection on MRI or EUS

• No residual luminal tumour following endoscopic resection

• Contraindications to radiotherapy including previous pelvic radiotherapy

• Uncontrolled cardiorespiratory comorbidity (includes patients with inadequately controlled angina or myocardial infarction within 6 months prior to randomisation)

• Known dihydropyrimidine dehydrogenase (DPYD) deficiency

• Known Gilberts disease (hyperbilirubinaemia)

• Taking warfarin that cannot be discontinued at least 7 days prior to starting treatment or substituted by low molecular weight heparin