We present a two-stage phase I/II design of a combination of two drugs in cancer clinical trials. The goal is to estimate safe dose combination regions with a desired level of efficacy. In stage I, conditional escalation with overdose control is used to allocate dose combinations to successive cohorts of patients and the maximum tolerated dose curve is estimated as a function of Bayes estimates of the model parameters. In stage II, we propose a Bayesian adaptive design for conducting the phase II trial to determine dose combination regions along the MTD curve with a desired level of efficacy. The methodology is evaluated by extensive simulations and application to a real trial.

中文翻译：

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使用细胞毒性药物的连续剂量组合进行 I-II 期癌症临床试验的两阶段设计。


我们在癌症临床试验中提出了两种药物组合的两阶段 I/II 期设计。目标是估计具有所需功效水平的安全剂量组合区域。在第一阶段，使用过量控制的条件升级将剂量组合分配给连续的患者组，并根据模型参数的贝叶斯估计来估计最大耐受剂量曲线。在第二阶段，我们提出了贝叶斯自适应设计来进行第二阶段试验，以确定沿 MTD 曲线的剂量组合区域，并具有所需的功效水平。该方法通过广泛的模拟和实际试验的应用进行评估。