Funding for this research was provided by:
Received: 27 November 2018
Accepted: 2 September 2019
First Online: 10 September 2019
Ethics approval and consent to participate
: All studies will be performed compliant with current standards of ICH GCP, the WHO Declaration of Helsinki and in accordance with the Medical Research Involving Human Subjects Act (WMO). The study protocols of all three trials are approved by the METC (Medisch-Ethische Toetsingscommissie, medical ethics committee) of The Netherlands Cancer Institute, Amsterdam, The Netherlands. All past and future protocol modifications are, or will be, submitted as amendments to the METC for approval. Most recent approved protocol versions are: version 6.0 dated June 23, 2014 for the NSCLC trial, version 6.0 dated March 08, 2017 for the breast cancer trial, and version 5.0 dated March 28, 2018 for the HNSCC trial. Patients receive both oral and written information on the study from their treating physician. Written informed consent is obtained before any study procedures. An optional part in the breast cancer trial and HNSCC trial involves genetic analysis. For patients that choose to take part of this analysis, there is a possibility of detection of unsolicited findings, i.e. germline DNA variants that confer an increased risk of developing malignancies or other diseases for both the patient and his/her family. Patients are informed about this possibility, and will be offered genetic counseling in case of revelation of a variant which is clinically relevant. A separate patient information file and consent form is used for this optional part of the study. Genetic analysis will only be performed in patients that give consent to performing genetic analysis AND to being informed on any unsolicited findings with clinical significance that have direct consequences for treatment or that are directly actionable (e.g. pathogenic mutations in BRCA1/2 genes). Patients can choose to be informed on unsolicited findings with clinical significance that are not directly actionable (e.g. carrier of an autosomal recessive disease). The complete study team at The Netherlands Cancer Institute will have access to the final trial dataset. The Netherlands Cancer Institute has a liability insurance that provides cover for damage to research subjects through injury or death as a result of participation in either one of the described studies. Trial results will be published in a major, peer-reviewed journal. Co-authors will include members of the protocol writing committee and physicians that have a substantial contribution in the conduct of the trial. AstraZeneca will be provided draft copies of all publications to review one month before submission. ExternalRef removed registration was done on March 23, 2012 for the NSCLC trial, on August 27, 2014 for the breast cancer trial, and on September 1, 2014 for the HNSCC trial. The first patient was enrolled at June 06, 2012 in the NSCLC trial, at October 21, 2013 in the breast cancer trial, and at September 09, 2014 in the HNSCC trial. All three trials are currently ongoing. Secondary identifying trial numbers are: UnorderedList removed
: Not applicable.
: JS, MV and CV filed a patent for the ‘REP-assay’ used in the trials. GS receives institutional research support from AstraZeneca and Merck. MvdH receives institutional research support from AstraZeneca.