背景:在消化道癌症中使用奥沙利铂可引起严重的周围神经病变(OIPN),降低患者和幸存者的生活质量。目前,对这些周围神经病变没有明确的治疗。多奈哌齐,一种可逆性的胆碱酯酶抑制剂,用于治疗老年痴呆症和痴呆症,据报道在人类中具有良好的安全性,临床前数据为其在OIPN动物模型中减少神经性症状和相关合并症的有效性提供了初步证据。
方法:DONEPEZOX试验将是一个概念验证,随机化,三盲,和多中心研究。这将是第一个评估多奈哌齐治疗OIPN的疗效和安全性的临床试验。根据QLQ-CIPN20感觉评分报告感觉神经病变的患有OIPN的成年癌症幸存者(相当于2级),在奥沙利铂为基础的化疗结束后至少6个月将包括在内.80名患者将被随机分配接受多奈哌齐或安慰剂治疗16周。主要终点将是多奈哌齐臂中的响应者的比率(根据QLQ-CIPN20感觉评分的神经性等级降低)。OIPN的严重程度将在治疗16周之前和之后通过QLQ-CIPN20感觉量表进行评估。与安慰剂组的比较将是次要目标。其他次要终点将是对多奈哌齐的耐受性,治疗前后各臂OIPN的严重程度和特征,相关的合并症和生活质量。Fleming的单阶段设计将用于样本量估计。对于多奈哌齐臂中至少30%的响应者率,该设计产生0.0417的I型错误率和91%的功率。计划总共80名随机患者。
结论:这项研究将允许,在积极结果的情况下,启动一项3期随机和安慰剂对照(主要终点)临床研究,以评估多奈哌齐治疗OIPN的治疗价值。
背景:NCT05254639,clincialtrials.gov,2022年2月24日注册。
BACKGROUND: The use of oxaliplatin in digestive tract cancers could induce severe peripheral neuropathy (OIPN) decreasing the quality of life of patients and survivors. There is currently, no univocal treatment for these peripheral neuropathies. Donepezil, a reversible inhibitor of cholinesterase, used to treat Alzheimer\'s disease and dementia, is reported to have a good safety profile in humans, and preclinical data have provided initial evidence of its effectiveness in diminishing neuropathic symptoms and related comorbidities in OIPN animal models.
METHODS: The DONEPEZOX
trial will be a proof-of-concept, randomised, triple-blinded, and multicentre
study. It will be the first clinical
trial evaluating the efficacy and safety of donepezil for the management of OIPN. Adult cancer survivors with OIPN that report sensory neuropathy according to QLQ-CIPN20 sensory score (equivalence of a grade ≥ 2), at least 6 months after the end of an oxaliplatin-based chemotherapy will be included. Eighty patients will be randomly assigned to receive either donepezil or placebo over 16 weeks of treatment. The primary endpoint will be the rate of responders (neuropathic grade decreases according to the QLQ-CIPN20 sensory score) in the donepezil arm. The severity of OIPN will be assessed by the QLQ-CIPN20 sensory scale before and after 16 weeks of treatment. The comparison versus the placebo arm will be a secondary objective. The other secondary endpoints will be tolerance to donepezil, the severity and features of OIPN in each arm before and after treatment, related-comorbidities and quality of life. Fleming\'s one-stage design will be used for sample size estimation. This design yields a type I error rate of 0.0417 and power of 91% for a responder rate of at least 30% in donepezil arm. A total of 80 randomized patients is planned.
CONCLUSIONS: This
study will allow, in the case of positive results, to initiate a phase 3 randomized and placebo-controlled (primary endpoint) clinical
study to assess the therapeutic interest of donepezil to treat OIPN.
BACKGROUND: NCT05254639 , clincialtrials.gov, Registered 24 February 2022.