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A novel phase I/IIa design for early phase oncology studies and its application in the evaluation of MK-0752 in pancreatic cancer

Whitehead, John and Thygesen, Helene and Jaki, Thomas and Davis, S. and Halford, S. and Turner, H. and Cook, N. and Jodrell, Duncan (2012) A novel phase I/IIa design for early phase oncology studies and its application in the evaluation of MK-0752 in pancreatic cancer. Statistics in Medicine, 31 (18). pp. 1931-1943. ISSN 1097-0258

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The Cancer Research UK study CR0720-11 is a trial to determine the tolerability and effect on survival of using two agents in combination in patients with advanced pancreatic cancer. In particular, the trial is designed first to identify the most suitable combination of doses of the two agents in terms of the incidence of dose-limiting toxicities. Then, the survival of all patients who have received that dose combination in the study so far, together with additional patients assigned to that dose combination to ensure that the total number is sufficient, will be analysed. If the survival outcomes show promise, then a definitive randomised study of that dose combination will be recommended. The first two patients in the trial will be treated with the lowest doses of each agent in combination. An adaptive Bayesian procedure based only on monotonicity constraints concerning the risks of toxicity at different dose levels will then be used to suggest dose combinations for subsequent patients. The survival analysis will concern only patients who received the chosen dose combination, and will compare observed mortality with that expected from an exponential model based on the known survival rates associated with current treatment. In this paper, the Bayesian dose-finding procedure is described and illustrated, and its properties are evaluated through simulation. Computation of the appropriate sample size for the survival investigation is also discussed.

Item Type: Journal Article
Journal or Publication Title: Statistics in Medicine
Uncontrolled Keywords: adaptive design ; Bayesian procedure ; combination therapies ; dose finding ; pancreatic cancer ; phase I/II design
Subjects: ?? qa ??
Departments: Faculty of Science and Technology > Mathematics and Statistics
ID Code: 54618
Deposited By: ep_importer_pure
Deposited On: 28 May 2012 11:53
Refereed?: Yes
Published?: Published
Last Modified: 13 Apr 2018 02:10
Identification Number:

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