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Implementing the time-to-event continual reassessment method in the presence of partial orders in a phase I head and neck cancer trial.
Patel, Amit; Brock, Kristian; Slade, Daniel; Gaunt, Claire; Kong, Anthony; Mehanna, Hisham; Billingham, Lucinda; Gaunt, Piers.
Afiliación
  • Patel A; Cancer Research Clinical Trials Unit, University of Birmingham, Birmingham, UK. a.patel.13@bham.ac.uk.
  • Brock K; Cancer Research Clinical Trials Unit, University of Birmingham, Birmingham, UK.
  • Slade D; Cancer Research Clinical Trials Unit, University of Birmingham, Birmingham, UK.
  • Gaunt C; Oncology R&D, AstraZeneca, Cambridge, UK.
  • Kong A; Cancer Research Clinical Trials Unit, University of Birmingham, Birmingham, UK.
  • Mehanna H; Department of Oncology, King's College London, London, UK.
  • Billingham L; Cancer Research Clinical Trials Unit, University of Birmingham, Birmingham, UK.
  • Gaunt P; Institute of Head and Neck Studies and Education, University of Birmingham, Birmingham, UK.
BMC Med Res Methodol ; 24(1): 11, 2024 Jan 13.
Article en En | MEDLINE | ID: mdl-38218799
ABSTRACT

BACKGROUND:

In this article we describe the methodology of the time-to-event continual reassessment method in the presence of partial orders (PO-TITE-CRM) and the process of implementing this trial design into a phase I trial in head and neck cancer called ADePT-DDR. The ADePT-DDR trial aims to find the maximum tolerated dose of an ATR inhibitor given in conjunction with radiotherapy in patients with head and neck squamous cell carcinoma.

METHODS:

The PO-TITE-CRM is a phase I trial design that builds upon the time-to-event continual reassessment method (TITE-CRM) to allow for the presence of partial ordering of doses. Partial orders occur in the case where the monotonicity assumption does not hold and the ordering of doses in terms of toxicity is not fully known.

RESULTS:

We arrived at a parameterisation of the design which performed well over a range of scenarios. Results from simulations were used iteratively to determine the best parameterisation of the design and we present the final set of simulations. We provide details on the methodology as well as insight into how it is applied to the trial.

CONCLUSIONS:

Whilst being a very efficient design we highlight some of the difficulties and challenges that come with implementing such a design. As the issue of partial ordering may become more frequent due to the increasing investigations of combination therapies we believe this account will be beneficial to those wishing to implement a design with partial orders. TRIAL REGISTRATION ADePT-DDR was added to the European Clinical Trials Database (EudraCT number 2020-001034-35) on 2020-08-07.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proyectos de Investigación / Neoplasias de Cabeza y Cuello Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: BMC Med Res Methodol Asunto de la revista: MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proyectos de Investigación / Neoplasias de Cabeza y Cuello Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: BMC Med Res Methodol Asunto de la revista: MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Reino Unido