An international multicentre randomised, feasibility study comprising a 1:1:1 randomisation for eligible subjects with a small, clinically localised rectal cancer between; (a) conventional TME Surgery, (b) organ saving with Chemoradiotherapy ± transanal microsurgery and (b) Short course preoperative radiotherapy ± transanal microsurgery.

   

Countries: Denmark, Netherlands and United Kingdom

The University of Birmingham is acting as sponsor for the trial, with co-ordination of the trial delegated to the Birmingham Clinical Trials Unit (BCTU). The BCTU acts as the International Coordinating Centre for the trial, with each collaborating country adopting a Hub and Spoke model, whereby the Hub is delegated defined sponsor oversight responsibilities.

UK funding is from CRUK (Clinical Trials Awards & Advisory Committee – Feasibility Study). The international sites, Denmark and the Netherlands, have secured their own independent funding from the Danish Cancer Society and Dutch Cancer Society respectively.

The University of Birmingham is contracting with each participating Hub. Each Hub is then responsible to contract with their in-country spoke hospitals. The University of Birmingham contracted with each participating research site in the UK.

The University of Birmingham has put in place insurance for legal liability for claims for injury arising from the Trial and where the University of Birmingham was at fault e.g. due to an error in the protocol. International sites are responsible for ensuring appropriate insurance or indemnity for clinical negligence is in place in their respective country and in relation to their clinical activities related to the trial.

Participating international sites were contractually required to obtain required local approvals as per local regulations. Evidence of local approvals are collected by the BCTU, prior to the site being confirmed as open to recruitment. International sites were responsible for local safety reporting as per local regulations.

One single protocol was used for both UK and international sites, with country-specific requirements included as necessary (this primarily concerned pharmacovigilance).

Although central monitoring processes are being utilised, on-site monitoring will also be conducted. The BCTU will perform on-site monitoring of UK sites if triggered. The Hubs are responsible for the on-site monitoring of their Spoke hospitals.

Participating sites had to have the ability to perform all four trial interventions in order to take part in the trial therefore no surgical or radiotherapy equipment was provided for trial purposes. The international sites were provided with electronic copies of all the Case Report Forms (CRFs) required for the trial.

All data for the trial is captured on paper CRFs. All hubs/sites send original copies of completed CRFs directly to the STAR-TREC trial team at BCTU, where this data is entered onto the trial database by dedicated trials staff. The BCTU will send any data queries raised by central monitoring to the Hub sites for resolution.

To enable a central pathological review, sites are required to send either glass sides or a duplicate set of H&E slides of the diagnostic pre-operative biopsy and any resected tumour should be prepared and sent to the national STAR-TREC trial office along with a copy of the pathology report. Site are also required to send paraffin embedded blocks of the diagnostic tissue biopsies and a FFPE tumour block and normal mucosal block from the primary tumour site for patients undergoing either trans anal microsurgery or TME. Patients are invited to provide optional consent for samples collected within the remit of the STAR-TREC Trial to be used for future research.

Validated translations of patient completed quality of life questionnaires have been used where available and combined into a booklet for each required time point, along with instructions for completion. The questionnaires used numerical scales and tick boxes (rather than free text fields) and the translated questionnaire booklets were laid out in an identical manner to the UK to facilitate data entry at the Clinical Trials Research Unit. There is no health economic analysis.

The trial data will be owned by the University of Birmingham as host institution. The main trial publication will be published in the name of the “STAR-TREC Collaborative Group”. All collaborators will be listed as contributors.