CONCORDE: A phase I platform study of novel agents in combination with conventional radiotherapy in non-small-cell lung cancer

Gerard M Walls, Jamie B Oughton, Anthony J Chalmers, Sarah Brown, Fiona Collinson, Martin D Forster, Kevin N Franks, Alexandra Gilbert, Gerard G Hanna, Nicola Hannaway, Stephen Harrow, Tom Haswell, Crispin T Hiley, Samantha Hinsley, Matthew Krebs, Geraldine Murden, Rachel Phillip, Anderson J Ryan, Ahmed Salem, David Sebag-Montefoire, Paul Shaw, Chris J Twelves, Katrina Walker, Robin J Young, Corinne Faivre-Finn, Alastair Greystoke, Gerard M Walls, Jamie B Oughton, Anthony J Chalmers, Sarah Brown, Fiona Collinson, Martin D Forster, Kevin N Franks, Alexandra Gilbert, Gerard G Hanna, Nicola Hannaway, Stephen Harrow, Tom Haswell, Crispin T Hiley, Samantha Hinsley, Matthew Krebs, Geraldine Murden, Rachel Phillip, Anderson J Ryan, Ahmed Salem, David Sebag-Montefoire, Paul Shaw, Chris J Twelves, Katrina Walker, Robin J Young, Corinne Faivre-Finn, Alastair Greystoke

Abstract

Lung cancer is the leading cause of cancer mortality worldwide and most patients are unsuitable for 'gold standard' treatment, which is concurrent chemoradiotherapy. CONCORDE is a platform study seeking to establish the toxicity profiles of multiple novel radiosensitisers targeting DNA repair proteins in patients treated with sequential chemoradiotherapy. Time-to-event continual reassessment will facilitate efficient dose-finding.

Keywords: ATM, Ataxia telangiectasia mutated; ATR, Ataxia telangiectasia and Rad3 related; CRT, Chemoradiotherapy; CT, Computed tomography; CTCAE, Common terminology criteria for adverse events; CTRad, Clinical and Translational Radiotherapy Research Working Group; Continual reassessment method; DDRi, DNA damage response inhibitor; DLT, Dose limiting toxicity; DNA damage repair inhibitor; DNA, Deoxyribonucleic acid; DNA-PK, DNA-dependent protein kinase; ECOG, Eastern Cooperative Oncology Group; EORTC, European Organisation for Research and Treatment of Cancer; ICRU, International Commission on Radiation Units and Measurements; IMPs, Investigational medicinal products; LA, Locally advanced; MRC, Medical Research Council; NCRI, National Cancer Research Institute; NSCLC, Non-small cell lung cancer; Non-small cell lung cancer; PARP, Poly (ADP-ribose) polymerase; PET, Positron emission tomography; PFS, Progression free survival; PROMs, Patient-reported outcome measures; Platform trial; RECIST, Response evaluation criteria in solid tumours; RP2D, Recommended phase II dose; RT, Radiotherapy; SACT, Systemic anti-cancer therapy; SRC, Safety review committee; Sequential chemoradiotherapy; TNM, Tumour node metastasis; TiTE-CRM, Time to event continual reassessment method; cfDNA, Cell-free DNA.

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

© 2020 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.

Figures

Fig. 1
Fig. 1
CONCORDE study summary.

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