Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

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, Séan M., Davis, Steven, Holmes, Jane, Brown, Richard, Fisher, Kerry, Seymour, Leonard, Adams, Richard, Good, James, Sebag-Montefiore, David, Maughan, Tim and Hawkins, Maria A. 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. 10.1186/s13014-020-01593-5

[thumbnail of s13014-020-01593-5.pdf] PDF - Published Version
Available under License Creative Commons Attribution.

Download (745kB)

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Centre for Trials Research (CNTRR)
Publisher: BioMed Central
ISSN: 1748-717X
Date of First Compliant Deposit: 13 May 2021
Date of Acceptance: 8 June 2020
Last Modified: 13 May 2021 15:30
URI: https://orca.cardiff.ac.uk/id/eprint/141032

Citation Data

Cited 5 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics