The STAR trial protocol: a randomised multi-stage phase II/III study of Sunitinib comparing temporary cessation with allowing continuation, at the time of maximal radiological response, in the first-line treatment of locally advanced/metastatic Renal Cancer
The STAR trial protocol: a randomised multi-stage phase II/III study of Sunitinib comparing temporary cessation with allowing continuation, at the time of maximal radiological response, in the first-line treatment of locally advanced/metastatic Renal Cancer
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DOI：
10.1186/1471-2407-12-598
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发表时间：
2012-12-14
期刊：
影响因子：
3.8
通讯作者：
Brown, Janet
中科院分区：
文献类型：
--
作者：
Collinson, Fiona J.;Gregory, Walter M.;Brown, Janet
背景：近年来，一些新的治疗方法在晚期肾细胞癌(RCC)中显示出良好的前景。在国际上，一线治疗的标准是舒尼替尼T，在被证明比干扰素-a有明显的生存益处后。惯例规定，假定患者可以耐受，舒尼替尼将一直持续到疾病进展的证据出现为止，尽管没有证据表明这种方法优于间歇性治疗。STAR试验的目的是比较标准治疗策略(常规持续策略，CCS)和包括计划治疗中断的新型无药物间隔策略(DFIS)。方法/设计：STAR试验是由NIHR HTA资助的英国实用随机II/III期临床试验，用于晚期肾癌的一线治疗。参与者将被随机(1：1)接受舒尼替尼CCS或DFIS。试验的总体目标是确定与CCS相比，DFIS在2年总生存期(OS)和质量调整寿命年(QALY)(治疗和随访期间的平均水平)方面是否是非劣质的。选择QALY主要终点来评估OS方面的任何损害是否可以与生活质量(QOL)的改善相平衡。这是一项具有许多设计挑战的复杂试验，为了解决这些问题，在试验设计中纳入了可行性阶段。必须满足预先确定的招募(阶段A)和疗效(阶段B)中间终点，以便能够继续进行整个第三阶段试验(阶段C)。在可行性阶段，将进行一项完整的定性患者偏好和理解研究，以调查患者对参与或不参与试验的感受。讨论：晚期肾癌患者继续服用舒尼替尼的最佳持续时间尚不清楚。新的靶向治疗对治疗持续时间的限制并不总是与标准化疗药物相同，目前还没有比较不同治疗持续时间的随机数据。合并计划的治疗间歇有可能改善生活质量和成本效益，希望不会对OS造成重大损害，就像在其他癌症类型和其他治疗方法中所证明的那样。
Background: Over recent years a number of novel therapies have shown promise in advanced renal cell carcinoma (RCC). Internationally the standard of care of first-line therapy is sunitinib T, after a clear survival benefit was demonstrated over interferon-a. Convention dictates that sunitinib is continued until evidence of disease progression, assuming tolerability, although there is no evidence that this approach is superior to intermittent periods of treatment. The purpose of the STAR trial is to compare the standard treatment strategy (conventional continuation strategy, CCS) with a novel drug free interval strategy (DFIS) which includes planned treatment breaks.Methods/Design: The STAR trial is an NIHR HTA-funded UK pragmatic randomised phase II/III clinical trial in the first-line treatment of advanced RCC. Participants will be randomised (1:1) to either a sunitinib CCS or a DFIS. The overall aim of the trial is to determine whether a DFIS is non-inferior, in terms of 2-year overall survival (OS) and quality adjusted life years (QALY) (averaged over treatment and follow up), compared to a CCS. The QALY primary endpoint was selected to assess whether any detriment in terms of OS could be balanced with improvements in quality of life (QoL). This is a complex trial with a number of design challenges, and to address these issues a feasibility stage is incorporated into the trial design. Predetermined recruitment (stage A) and efficacy (stage B) intermediary endpoints must be met to allow continuation to the overall phase III trial (stage C). An integral qualitative patient preference and understanding study will occur alongside the feasibility stage to investigate patients' feelings regarding participation or non-participation in the trial.Discussion: The optimal duration of continuing sunitinib in advanced RCC is unknown. Novel targeted therapies do not always have the same constraints to treatment duration as standard chemotherapeutic agents and currently there are no randomised data comparing different treatment durations. Incorporating planned treatment breaks has the potential to improve QoL and cost effectiveness, hopefully without significant detriment on OS, as has been demonstrated in other cancer types with other treatments.