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).

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  • Additional Information
    • Affiliation:
      Oxford Institute of Radiation Oncology, University of Oxford, OX3 7LE, Oxford, UK
      Department of Oncology, University of Oxford, OX3 7LE, Oxford, UK
      Centre for Statistical Medicine, University of Oxford, OX3 7LE, Oxford, UK
      PsiOxus Therapeutics, Barton Lane, OX14 3YS, Abingdon, UK
      Velindre Cancer Centre, CF14 2TL, Cardiff, UK
      Queen Elizabeth Hospital Birmingham, Edgbaston, B15 2GW, Birmingham, UK
      Department of Clinical Oncology, University of Leeds, Leeds Cancer UK Centre, Leeds, UK
      Department of Physics and Biomedical Engineering, University College London, Oxford, UK
    • 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.
    • Journal Subset:
      Biomedical; Europe; UK & Ireland
    • ISSN:
      1748-717X
    • MEDLINE Info:
      PMID: NLM32532291 NLM UID: 101265111
    • Grant Information:
      C43735/A24474//Cancer Research UK/United Kingdom
    • Publication Date:
      In Process
    • Publication Date:
      20200617
    • DOI:
      10.1186/s13014-020-01593-5
    • Accession Number:
      143738235
  • Citations
    • ABNT:
      O’CATHAIL, S. M. et al. 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, [s. l.], v. 15, n. 1, p. 1–8, 2020. DOI 10.1186/s13014-020-01593-5. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=143738235. Acesso em: 26 nov. 2020.
    • AMA:
      O’Cathail SM, Davis S, Holmes J, et al. 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. 2020;15(1):1-8. doi:10.1186/s13014-020-01593-5
    • APA:
      O’Cathail, S. M., Davis, S., Holmes, J., Brown, R., Fisher, K., Seymour, L., Adams, R., Good, J., Sebag-Montefiore, D., Maughan, T., & Hawkins, M. 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(1), 1–8. https://doi.org/10.1186/s13014-020-01593-5
    • Chicago/Turabian: Author-Date:
      O’Cathail, Séan M., Steven Davis, Jane Holmes, Richard Brown, Kerry Fisher, Leonard Seymour, Richard Adams, 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 (1): 1–8. doi:10.1186/s13014-020-01593-5.
    • Harvard:
      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(1), pp. 1–8. doi: 10.1186/s13014-020-01593-5.
    • Harvard: Australian:
      O’Cathail, SM, Davis, S, Holmes, J, Brown, R, Fisher, K, Seymour, L, Adams, R, Good, J, Sebag-Montefiore, D, Maughan, T & Hawkins, MA 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, vol. 15, no. 1, pp. 1–8, viewed 26 November 2020, .
    • MLA:
      O’Cathail, Séan M., et al. “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, vol. 15, no. 1, June 2020, pp. 1–8. EBSCOhost, doi:10.1186/s13014-020-01593-5.
    • Chicago/Turabian: Humanities:
      O’Cathail, Séan M., Steven Davis, Jane Holmes, Richard Brown, Kerry Fisher, Leonard Seymour, Richard Adams, et al. “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, no. 1 (June 12, 2020): 1–8. doi:10.1186/s13014-020-01593-5.
    • Vancouver/ICMJE:
      O’Cathail SM, Davis S, Holmes J, Brown R, Fisher K, Seymour L, et al. 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 [Internet]. 2020 Jun 12 [cited 2020 Nov 26];15(1):1–8. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=143738235