University of Massachusetts Medical School, Worcester, Massachusetts.
Harvard Medical School, Boston, Massachusetts.
Pediatr Blood Cancer. 2020 Nov;67(11):e28694. doi: 10.1002/pbc.28694. Epub 2020 Sep 4.
Understanding trends in characteristics of early phase trials that allow minors with cancer to participate may inform additional efforts to improve cancer drug development for young people.
We accessed data for oncology phase 1 or phase 1/2 trials in the United States from ClinicalTrials.gov with lower age bound for eligibility <18 years. Descriptive statistics were calculated and trends over time evaluated using logistic and multinomial logistic regression.
Six hundred twelve trials met inclusion criteria. Sixty-five percent of trials were for older adults that also allowed minors, while 9% were exclusively for patients ≤18 years of age. Eighty-three percent of trials included at least one novel agent, while 17% studied only conventional therapies. Fifty-eight percent of trials studied treatments not yet Food and Drug Administration (FDA) approved (48% if exclusively for patients ≤18 years). Fifteen percent of trials for which dose-escalation method could be determined, utilized a model-based design. Eighteen percent of all trials were industry sponsored (48% if exclusively for patients ≤18 years). Forty-nine percent of all trials were multicenter (69% if exclusively for patients ≤18 years). There was an increase in trials exclusively focused on patients with central nervous system (CNS) tumors over the study period (P ≤ .02). No other temporal trends were seen. The median times from first-in-adult to first-in-pediatric for monotherapy and combination trials were 5.7 and 3.3 years, respectively.
The paucity of clear temporal trends highlights the need for innovation in early drug development for young people. Our analysis serves as a benchmark against which to evaluate initiatives to improve pediatric cancer drug development.
了解允许癌症患儿参与的早期试验特征趋势，可能为进一步努力改善年轻人癌症药物开发提供信息。
我们从 ClinicalTrials.gov 获取了美国肿瘤学 1 期或 1/2 期试验的数据，其纳入标准为年龄下限 <18 岁。计算描述性统计数据，并使用逻辑和多项逻辑回归评估随时间的趋势。
符合纳入标准的试验有 612 项。65%的试验是针对年龄较大的患者且允许未成年患者参加，而 9%的试验仅针对 ≤18 岁的患者。83%的试验至少包括一种新的药物，而 17%的试验仅研究常规疗法。58%的试验研究尚未获得食品和药物管理局（FDA）批准的治疗方法（如果仅针对 ≤18 岁的患者，则为 48%）。在可以确定剂量递增方法的 15%的试验中，采用了基于模型的设计。18%的试验由工业界赞助（如果仅针对 ≤18 岁的患者，则为 48%）。49%的试验为多中心试验（如果仅针对 ≤18 岁的患者，则为 69%）。在研究期间，专门针对中枢神经系统（CNS）肿瘤患者的试验数量有所增加（P≤.02）。未观察到其他时间趋势。单药和联合试验中，首次在成人中进行到首次在儿科中进行的中位时间分别为 5.7 年和 3.3 年。
缺乏明确的时间趋势突出表明需要在年轻人的早期药物开发方面进行创新。我们的分析可作为评估改善儿科癌症药物开发计划的基准。
