FAQ

Q1A: When consenting a patient to the registration part how in date do the pre-registration laboratory tests need to be?
A: We don’t provide a timeframe in the protocol as we didn’t want to be too restrictive. We ask that these bloods are done in a reasonable timeframe prior to registration to confirm the participant is eligible to be registered. We suggest that pre-registration blood tests within 2 months is reasonable.

Q2A: The participant needs to have a measurable lesion by the RECIST criteria, but you do not actually need a RECIST report from our radiologists?
A: No. The CT scan needs to be possible to report to RECIST criteria but doesn’t need to be RECIST reported at the recruiting site, as scans will be reviewed and measured centrally in order to determine the primary outcome of early tumour shrinkage.

Q3A: Can the baseline ctDNA which the protocol states should be taken between reg/rand, be taken post-randomisation but before start of trial treatment if it was missed in error?
A: Yes this is allowed, as long as it is taken before the patient starts treatment.

Q4A: Can the cycle 1 of chemotherapy that’s allowed pre randomisation include anti EGFR agents?
A: Only if this is the current standard approach.

Q1B: How are cetuximab/panitumumab drugs funded currently?
A: These are currently funded by Blue-Teq.

Q2B: Is bevacizumab reimbursed for patients on ARIEL?
A: At the point of this protocol bevacizumab is not reimbursed by NICE.

Q1C: What is the justification for including BRAF mutant patients?
A: Accumulated retrospective data suggest either no significant benefit or potential harm from EGFR inhibitors in this group of patients (when not combined with a BRAF inhibitor). There is additional interesting data to suggest that there are three types of BRAF mutation and one of these groups may well be responsive to EGFR therapy.

Q2C: If a patient has a CT contrast allergy, could we use CT without contrast or MRI instead?
A: For the patient to be eligible for the trial they need to have measurable lesions on imaging. If there are measurable lesions on no contrast CT (assuming they cannot have contrast because of prior reaction) then they can enter the trial. However, if they have disease that is only visible on MRI and the site cannot offer contrast CT for follow up then that patient would not be eligible to enter the trial.

Q3C: Can patient be co-enrolled in other studies?
A: As long as the study is non interventional then this should be fine, but please contact the CTRU for confirmation.

Q1D: If we usually use our local pathway for processing of RAS/BRAF samples, are we allowed to use the central lab if there are delays locally?
A: Yes. The central lab can be used for all your RAS/BRAF sample processing or on an ad hoc basis if there are delays locally.

Q2D: If a patient has consented to further translational research, but the remaining sample had little to no diagnostic material, should the sample still be sent to the Leeds lab?
A: In these cases, the sample does not need to be sent to Leeds. Please let CTRU know if the patient has consented but there is not enough material for future translational research.

Q3D: Should we collect a ctDNA sample if the patient is not going to be randomised?
A: Yes. We are intentionally collecting ctDNA samples from all registered patients and would like to collect samples from as many of the registered patients as possible. If the baseline sample is missed for consented patients, there is no need to collect the sample for week 16. For consented patients, if the sample is missed pre-randomisation, the sample can be taken post-randomisation but before cycle 1.

Q4D: How do we order more supplies for sending the tumour samples to the labs?
A: The packaging supplies and eppendorf tubes to send tumour samples to Birmingham for EREG/AREG testing should be supplied by sites, as should the packaging materials for any samples sent to Leeds for RAS testing or for sectioning. The blood collection kits for sending ctDNA samples to Birmingham are provided by the Birmingham team and can be requested from ariel-samples@lists.bham.ac.uk. You should have enough supplies in stock for one patient, and more kits should only be requested when you are registering a new patient.

Q1E: Does recruitment count at registration or randomisation for uploading onto EDGE/LPMS?
A: Recruitment should be counted from when consent is taken and the patient has been registered. Our recruitment policy states data should be provided for each recruit that has consented to participate during the study. If participants later become randomised, they will have already been uploaded and counted.

Q2E: What is the study end date?
A: Following the approval for an extension by the NIHR, the current predicted end date for recruitment is 31/08/2025. The planned end date including follow up any analysis will be 31/03/2027.

Q1F: Should we send originals or photocopies of Quality-of-Life booklets?
A: Please send originals. Copies of QoL booklets should NOT be made or kept at site. We recommend that you complete the booklet header details before handing to the patient so that they can then seal in the envelope.