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

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.

Abbreviations

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