A phase 1 trial of the safety, tolerability and biological effects of intravenous Enadenotucirev, a novel oncolytic virus, in combination with chemoradiotherapy in locally advanced rectal cancer (CEDAR)

O'Cathail, S. M. et al. (2020) A phase 1 trial of the safety, tolerability and biological effects of intravenous Enadenotucirev, a novel oncolytic virus, in combination with chemoradiotherapy in locally advanced rectal cancer (CEDAR). Radiation Oncology, 15, 151. (doi: 10.1186/s13014-020-01593-5) (PMID:32532291) (PMCID:PMC7291514)

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Abstract

Background: Chemoradiotherapy remains the standard of care for locally advanced rectal cancer. Efforts to intensify treatment and increase response rates have yet to yield practice changing results due to increased toxicity and/or absence of increased radiosensitization. Enadenotucirev (EnAd) is a tumour selective, oncolytic adenovirus which can be given intravenously. Pre-clinical evidence of synergy with radiation warrants further clinical testing and assessment of safety with radiation. Methods: Eligibility include histology confirmed locally advanced rectal cancer that require chemoradiation. The trial will use a Time-to-Event Continual Reassessment Model-based (TiTE-CRM) approach using toxicity and efficacy as co-primary endpoints to recommend the optimal dose and treatment schedule 30 patients will be recruited. Secondary endpoints include pathological complete response the neoadjuvant rectal score. A translational program will be based on a mandatory biopsy during the second week of treatment for ‘proof-of-concept’ and exploration of mechanism. The trial opened to recruitment in July 2019, at an expected rate of 1 per month for up to 4 years. Discussion: Chemoradiation with Enadenotucirev as a radiosensitiser in locally Advanced Rectal cancer (CEDAR) is a prospective multicentre study testing a new paradigm in radiosensitization in rectal cancer. The unique ability of EnAd to selectively infect tumour cells following intravenous delivery is an exciting opportunity with a clear translational goal. The novel statistical design will make efficient use of both toxicity and efficacy data to inform subsequent studies. Trial registration: ClinicalTrial.gov, NCT03916510. Registered 16th April 2019.

Item Type:Articles
Additional Information:The study is funded by Cancer Research UK and University of Oxford.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:O'Cathail, Dr Sean
Authors: O'Cathail, S. M., Davis, S., Holmes, J., Brown, R., Fisher, K., Seymour, L., Adams, R., Good, J., Sebag-Montefiore, D., Maughan, T., and Hawkins, M. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Radiation Oncology
Publisher:BioMed Central
ISSN:1748-717X
ISSN (Online):1748-717X
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Radiation Oncology 15: 151
Publisher Policy:Reproduced under a Creative Commons License

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