The ACT-ONE trial, a multicentre, randomised, double-blind, placebo-controlled, dose-finding study of the anabolic/catabolic transforming agent, MT-102 in subjects with cachexia related to stage III and IV non-small cell lung cancer and colorectal cancer: study design
The ACT-ONE trial, a multicentre, randomised, double-blind, placebo-controlled, dose-finding study of the anabolic/catabolic transforming agent, MT-102 in subjects with cachexia related to stage III and IV non-small cell lung cancer and colorectal cancer: study design
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DOI：
10.1007/s13539-011-0046-2
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发表时间：
2011-12-01
影响因子：
8.9
通讯作者：
Anker, Stefan D.
中科院分区：
文献类型：
--
作者：
Coats, Andrew J. Stewart;Srinivasan, Venkatesan;Anker, Stefan D.
恶病质是一种与包括癌症在内的多种严重疾病相关的消耗性疾病，是发病率和死亡率的主要原因。目前没有广泛批准的治疗剂用于治疗或预防癌症相关的恶病质。结直肠癌和非小细胞肺癌的恶病质发生率相对较高，分别约为28%和34%。神经激素过度活跃与恶病质的发生和发展有关，β受体拮抗剂已被提出作为一种潜在的治疗方法。MT-102是一种新的合成代谢/分解代谢转化剂，对癌症恶病质中的三个潜在药理学靶点具有多功能作用，即通过非选择性β-阻断减少catalysis，通过中枢5-HT 1a拮抗减少疲劳和产热，以及通过部分β-2受体激动增加analysis。年龄在25 - 80岁之间，确诊为晚期非小细胞肺癌或结直肠癌，伴有恶病质的患者将以3：1：2的比例（MT-102 10 mg BD-1/MT-102 2.5 mg BD/安慰剂）随机分配至两种MT-102剂量之一或安慰剂组。患者将继续接受最长16周的研究治疗。按分配的治疗组分析的主要终点将是16周内的体重变化。对于该端点，这项研究有85%的把握（0.05%显著性水平），以检测每4周期间安慰剂组和高剂量MT-102组的平均变化为-0.8 kg和0 kg。第一例患者于2011年2月随机分配，患者招募预计将持续到2012年年中。分解代谢转化剂MT-102将对癌症恶病质中的体重变化率产生积极影响，从而评估这种迄今难以治疗的病症的新治疗策略。一项单独的ACT-TWO试验将招募完成ACT-ONE试验并继续接受随机双盲药物治疗的患者。ACT-TWO的参与者将接受额外的随访，并有单独的主要终点。
Aims Cachexia, the wasting disorder associated with a wide range of serious illnesses including cancer, is a major cause of morbidity and mortality. There is currently no widely approved therapeutic agent for treating or preventing cancer-associated cachexia. Colorectal cancer and non-small cell lung cancer have relatively high incidences of cachexia, approximately 28% and 34%, respectively. Neurohormonal overactivity has been implicated in the genesis and progression of cachexia and beta receptor antagonism has been proposed as a potential therapy. MT-102, a novel anabolic/catabolic transforming agent, has a multi-functional effect upon three potential pharmacological targets in cancer cachexia, namely reduced catabolism through non-selective beta-blockade, reduced fatigue, and thermogenesis through central 5-HT1a antagonism and increased anabolism through partial beta-2 receptor agonism.Methods At least 132 male and female patients, aged between 25 and 80 years with a confirmed diagnosis of late-stage non-small cell lung cancer or colorectal cancer, with cachexia will be randomised to either one of the two MT-102 doses or placebo in a 3: 1: 2 ratio (MT-102 10 mg BD-1/MT-102 2.5 mg BD/placebo). Patients will continue on study treatment for maximally 16 weeks. The primary endpoint, to be analysed by assigned treatment group, will be body weight change over 16 weeks. For this endpoint, the study has 85% power (0.05% significance level) to detect per 4-week period a mean change of -0.8 kg in the placebo group and 0 kg in the high-dose MT-102 arm. The first patient was randomised in February 2011 and patient recruitment is expected to continue until mid-2012.Perspective The ACT-ONE trial is designed to test whether the anabolic/catabolic transforming agent MT-102 will positively impact on the rate of change of body weight in cancer cachexia, thereby evaluating a novel therapeutic strategy in this hitherto poorly treatable condition. A separate ACT-TWO trial will recruit patients who complete the ACT-ONE trial and remain on randomised double-blind medication. Participants in ACT-TWO will be followed for an additional period with a separate primary endpoint.