Eligibility criteria for sites

For a site to be identified as being compliant with the inclusion criteria, a site evaluation form must be completed and the site may require a visit or teleconference from relevant members of the TMG to finalise their assesssment. Once this has been completed and level of site determined, the FOCUS4 team will provide the site with the FOCUS4 Trials Programme documentation for their R&D approval and MRC CTU accreditation documents. Sites must complete the FOCUS4 programme accreditation documentation at the same time as applying for their local R&D approval through the Integrated Research Application System (IRAS).

LEVEL 1 SITE INCLUSION CRITERIA

Requirements for all sites to participate as level 1 sites are as follows:
  • The institution regularly undertakes the treatment of patients with advanced or metastatic CRC
  • Patients must be under the care of a consultant medical or clinical oncologist
  • Willingness to refer patients in the higher risk trials onward to a level 2 or 3 site (where applicable) until the therapy is deemed to be sufficiently safe and appropriate for that patient. Identification of the most appropriate Level 2 or 3 site and agreement with that site to accept referrals for FOCUS4 (this may be on a patient by patient basis)
  • Agreement by the local pathology department that they will identify and send a FFPE block containing maximum viable tumour to the central laboratory. All participating sites will need to provide confirmation from the lead colorectal pathologist and/or Head of Histopathology Service that a FFPE tumour block will be released following patient registration and sent to the designated laboratory for central biomarker panel testing. To that end, an identified secretarial or technical contact person and their fax and telephone numbers and the name of the designated pathologist with their written agreement of participation will be required from all sites before being accredited to participate in the trial
  • For administration of the standard first-line chemotherapy, normal practice requirements should be followed. Treatment must be administered in a dedicated oncology facility where, in addition to specialist nursing and junior medical staff, the consultant medical or clinical oncologist is routinely on-site and available to discuss/assess patients prior to treatment. Defined arrangements must be in place for the management of acute complications of the standard chemotherapy in weeks 1-16. These may include admission to the designated facility at the site or Unit under the direct supervision of the consultant oncologist, haemato-oncology colleague or general medical service, but should not include admission under the surgical service
  • Pharmacy support for treatment allocation of novel therapies and trial administration. The FOCUS4 pharmacist will sign an agreement to confirm that local hospital systems are in place to cover drug ordering, drug receipt, drug storage and dispensing, and will enable accurate traceability of all drugs used in the trial
  • Research nurse support for informed consent and on trial data entry and collection. All Serious Adverse Events (SAEs) will be reported immediately to the MRC CTU (within one working day of the investigator becoming aware of the event). The initial SAE report shall be promptly followed by detailed written reports
  • The site has an adequate number of qualified staff and adequate facilities for the foreseen duration of FOCUS4 to conduct the trial properly and safely according to the FOCUS4 Trials Programme protocol
  • All staff assisting with FOCUS4 are adequately informed and trained about the FOCUS4 Trials Programme protocols, the investigational products and their FOCUS4 related duties. Staff will participate in mandatory initial and ongoing training for the FOCUS4 Trials Programme and each trial as required
  • FOCUS4 will be conducted in accordance with the current protocols
  • FOCUS4 will be conducted in compliance with the principles of GCP and all applicable regulatory requirements
  • The site will permit monitoring and auditing by the MRC CTU and inspection by the appropriate regulatory authorities and applicable pharmaceutical companies if required. Direct access will be made available to all trial related sites, data/documents and reports
  • The site will maintain a trial site file, which will contain essential documents for the conduct of the FOCUS4 Trials Programme
  • All FOCUS4 data will be submitted in a timely manner and as described in the protocol. Individual sites may be suspended from recruitment of new patients if data returns are poor or if trial conduct is violated in other ways
  • No trial data on FOCUS4 patients within their site will be disclosed without the approval of the TMG and Trial Steering Committee (TSC)
  • All documents related to the FOCUS4 Trials Programme will be retained for at least 10 years after the completion of the trial
  • The ability to be able to transfer CT scans electronically to other sites if required.

LEVEL 2 SITE INCLUSION CRITERIA

Requirements for a site to participate as a level 2 site in addition to the requirements of a level 1 site:
  • Experience with novel tyrosine kinase inhibitor (TKI) studies in phase 2 studies in the site
  • Willingness to refer patients in the higher risk trials onward to a level 3 site until the therapy is deemed to be sufficiently safe and appropriate for that patient to be treated at their level 2 site. Identification of the most appropriate level 3 site and agreement with that site to accept referrals for FOCUS4
  • Availability of relevant non-oncology specialists with named contacts including ophthalmology, dermatology and any other needed specialty input according to the agent toxicity profile
  • Willingness to accept referrals from level 1 sites.

LEVEL 3 SITE INCLUSION CRITERIA

Requirements for a site to participate as level 3 site includes all the requirements of the level 1 and 2 sites and in addition:
  • Experience of conducting phase 1 and early phase 2 trials including those of novel TKIs
  • Readiness and resource to attend additional monitoring Investigator teleconferences on a fortnightly or monthly basis when the first patients are being dosed
  • Willingness to accept referrals from level 1 and 2 sites.