The STAR-TREC Trial

STAR-TREC is an international, multi-centre, randomised, phase II feasibility study comprising a 1:1:1 randomisation for eligible subjects with a small, clinically localised rectal cancer between;

• ARM A: Conventional TME surgery
• ARM B: Organ saving utilising long course concurrent chemoradiation
• ARM C: Organ saving utilising short course preoperative radiotherapy

 A total of 120 patients will be randomised over 2 years.

• Recruitment rate

• Procurement of STAR-TREC funding by one international partner
• Opening of STAR-TREC by one international partner
• Efficacy of organ preserving treatment arm 

• Accuracy of MRI in predicting STAR-TREC eligibility
• 30-day mortality
• 6 month mortality
• Surgical morbidity
• Rate of tumour recurrence or regrowth within the bowel wall (experimental arm)
• Rate of tumour recurrence within the mesorectum (experimental arm)
• Rate of distant metastases
• Pelvic failure rate
• Bowel, bladder and sexual dysfunction
• Proportion of patients with / without a stoma at one year
• Histopathological assessment of tumour down-staging following radiotherapy
• Proportion of patients identified by clinical and MRI assessment as suitable for active monitoring
• Conversion rates from organ saving to radical surgery
• Disease free survival
• Quality of life
• Overall survival

STAR-TREC is open at hospitals in the UK, Netherlands and Denmark.

 Inclusion Criteria

• Biopsy proven adenocarcinoma of the rectum
• mriT1-3bN0 (with ≤5mm of mesorectal invasion) rectal tumour or endorectal ultrasound defined retal cancer uT1-uT3b
• MDT determines that all of the following treatment options are feasible (a) TMG surgery, (b) CRT, (c) SCPRT, (d) 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 in Netherlands and Denmark)
• (Pre-treatment) Estimated creatinine clearance >50mls/min
• (Pre-treatment) Absolute neutrophil count >1.5x109/l; platelets >100 x 109/L
• (Pre-treatment) Serum transaminase <3 x Upper Limit Normal/l (ULN)
• (Pre-treatment) Bilirubin <1.5 x ULN
• ECOG performance status 0-1
• (If female and of childbearing potential) 1. Negative pregnancy test ≤72hours prior to initiating study treatment; 2. Agree to avoid pregnancy during and for 6 months after study treatment
• (If male and with a partner of childbearing potential) Agree to use adequate, medically approved, contraceptive precautions during and for 90 days after the last dose of study treatment
• Able and willing to provide written informed consent

 Exclusion Criteria

• Unequivocal evidence of metastatic disease (includes resectable metastases)
• MRI node positive
• MRI extramural vascular invasion (mriEMVI) positive
• MRI defined mucinous tumour
• Mesorectal fascia threatened (≤1mm on MRI)
• Maximum tumour diameter >40mm as measured from everted edges on sagittal 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 resection
• Uncontrolled cardiorespiratory comorbidity (includes patients with inadequately controlled angina or myocardial infarction within 6 months prior to randomisation)
• Known dihydropyrimidine dehydrogenase (DYPD) 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
• Taking phenytoin or sorivudine or its chemically related analogues, such as brivudine (more details in protocol)
• Patients currently taking metronidazole
• Pregnant, lactating or pre-menopausal women not using adequate contraception
• History of severe and unexpected reactions to fluoropyrimidine therapy
• Unable or unwilling to provide written informed consent

Registering your interest and confirming participation in the STAR-TREC can be completed in three simple steps:

1. Discuss the study locally with the Surgeon, Radiologists, Pathologist, Oncologists and Research nurses.
2. Complete the STAR-TREC Trial Site Feasibility/Assessment & Registration form. 
3. Send the completed Site Feasibility/Assessment & Registration form to the STAR-TREC Study office along with:

1. • CV and GCP certificate of the potential Principal Investigator.
   • CV and GCP certificate of all those listed on the Site Feasibility/Assessment & Registration form.
   • CV and GCP certificate of all those listed on the Site Feasibility/Assessment & Registration form.