CONCORDE: A phase I platform study of novel agents in combination with conventional radiotherapy in non-small-cell lung cancer. (November 2020)

• Record Type: Journal Article
• Authors: Walls, Gerard M.; Oughton, Jamie B.; Chalmers, Anthony J.; Brown, Sarah; Collinson, Fiona; Forster, Martin D.; Franks, Kevin N.; Gilbert, Alexandra; Hanna, Gerard G.; Hannaway, Nicola; Harrow, Stephen; Haswell, Tom; Hiley, Crispin T.; Hinsley, Samantha; Krebs, Matthew; Murden, Geraldine; Phillip, Rachel; Ryan, Anderson J.; Salem, Ahmed; Sebag-Montefoire, David; Shaw, Paul; Twelves, Chris J.; Walker, Katrina; Young, Robin J.; Faivre-Finn, Corinne; Greystoke, Alastair
• Is Part Of: Clinical and translational radiation oncology. Volume 25(2020)
• Page Start: 61
• Page End: 66
• Publication Date: 2020-11
• Subjects: ATM Ataxia telangiectasia mutated -- ATR Ataxia telangiectasia and Rad3 related -- cfDNA Cell-free DNA -- CRT Chemoradiotherapy -- CT Computed tomography -- CTCAE Common terminology criteria for adverse events -- CTRad Clinical and Translational Radiotherapy Research Working Group -- DDRi DNA damage response inhibitor -- DLT Dose limiting toxicity -- 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 -- PARP Poly (ADP-ribose) polymerase -- PET Positron emission tomography -- PFS Progression free survival -- PROMs Patient-reported outcome measures -- RECIST Response evaluation criteria in solid tumours -- RP2D Recommended phase II dose -- RT Radiotherapy -- SACT Systemic anti-cancer therapy -- SRC Safety review committee -- TiTE-CRM Time to event continual reassessment method -- TNM Tumour node metastasis; Non-small cell lung cancer -- Sequential chemoradiotherapy -- DNA damage repair inhibitor -- Platform trial -- Continual reassessment method; Cancer -- Radiotherapy -- Periodicals; Oncology -- Periodicals; Cancer -- Radiotherapy; Oncology; Radiation Oncology; Neoplasms -- radiotherapy; Translational Medical Research; Periodicals; Electronic journals; Periodicals; 616.9940642
• DOI: 10.1016/j.ctro.2020.09.006
• Languages: English
• ISSNs: 2405-6308

Abstract

Highlights: Lung cancer is the leading cause of cancer mortality worldwide. Gold standard chemoradiotherapy is not deliverable for the majority of patients. Radiation-induced DNA damage repair is an actionable mechanism of radioresistance. Careful trial design is essential to elicit maximum impact on therapeutic index. CONCORDE is a platform study of novel drug/radiotherapy combinations in lung cancer. 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.