Phase 0 clinical trials: Conceptions and misconceptions
Phase 0 clinical trials: Conceptions and misconceptions
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DOI：
10.1097/ppo.0b013e318172d6f3
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发表时间：
2008-05-01
期刊：
影响因子：
2.2
通讯作者：
Doroshow, James H.
中科院分区：
文献类型：
--
作者：
Kummar, Shivaani;Rubinstein, Larry;Doroshow, James H.
0期临床试验是为了响应美国食品药品监督管理局（FDA）最近的探索性研究性新药（IND）指南而开发的，旨在加快新分子实体的临床评价。探索性IND支持基于降低的生产和毒理学要求，以亚治疗剂量对新研究药物进行首次人体试验，从而在临床开发早期证明药物-靶向效应并评估人体药代动力学-药效学关系。0期癌症临床试验的目的是在最早的时机-在大量患者累积并暴露于潜在的药物相关毒性之前-确定药物是否调节其在肿瘤中的靶点，从而确定是否需要进一步的临床开发。我们在这里回顾了探索性IND下进行的临床研究的基本要求，并解决了关于肿瘤0期试验的一些常见误解。
Phase 0 clinical trials, developed in response to the United States Food and Drug Administration (FDA)'s recent exploratory Investigational New Drug (IND) guidance, are intended to expedite the clinical evaluation of new molecular entities. The exploratory IND supports the performance of first-in-human testing of new investigational agents at subtherapeutic doses based on reduced manufacturing and toxicologic requirements, allowing the demonstration of drug-target effects and assessment of pharmacokinetic-pharmacodynamic relationships in humans earlier in clinical development. The objectives of a phase 0 cancer clinical trial are to establish at the very earliest opportunity-before large numbers of patients have been accrued and exposed to potential drug-associated toxicity-whether an agent is modulating its target in a tumor, and consequently whether further clinical development is warranted. We review here the fundamental requirements of clinical studies conducted under an exploratory IND and address some common misconceptions regarding oncologic phase 0 trials.