Regorafenib assessment in refractory advanced colorectal cancer: RegARd-C study protocol.
Regorafenib assessment in refractory advanced colorectal cancer: RegARd-C study protocol.
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DOI：
10.1136/bmjopen-2014-007189
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发表时间：
2015-03-09
期刊：
影响因子：
2.9
通讯作者：
Flamen P
中科院分区：
文献类型：
--
作者：
Hendlisz A;Deleporte A;Vandeputte C;Charette N;Paesmans M;Guiot T;Garcia C;Flamen P
瑞戈非尼最近被批准用于接受过治疗的晚期结直肠癌 (aCRC) 患者，尽管患者的预后有所改善，并且具有显着的毒性。先前的研究表明，基于早期氟脱氧葡萄糖正电子发射断层扫描 (FDG-PET) 的代谢反应评估 (MRA) 可能会充分选择不太可能从治疗中受益的患者，RegARd-C 试验利用早期 MRA 来识别 aCRC 患者群体中可能对瑞格非尼无反应的患者，并指导对治疗耐药的基因组和表观遗传决定因素进行综合评估。 RegARd-C 是一项多中心前瞻性研究。其主要目标是在接受过治疗的 aCRC 患者群体中，确定 4 周内 3 周、每天 160 毫克瑞格非尼治疗的非受益者。在第一个疗程的第 14 天重复基线 PET。 MRA 对调查人员是不知情的。总生存期 (OS) 是主要终点，与从肿瘤和系列血液样本评估的代谢参数和（表观）遗传改变相关。 105 名可评估患者的目标样本量（70 名作为推导集，35 名作为验证集）被认为足以验证代谢应答者 OS 的预期 HR 与代谢无应答者相比显着 <1（在真实 HR ≤ 0.59 且应答者率为 47% 的情况下，具有 80% 功效和单侧 5% α）。该研究得到了 Jules Bordet 研究所主管伦理委员会的批准，符合赫尔辛基宣言或比利时法律法规（以为患者提供最大保护的为准），并遵循国际协调会议 E 6 (R1) 良好临床实践指南，参考号 CPMP/ICH/135/95。该方案和试验结果，即使是不确定的，也将在国际肿瘤学大会上提出，并在同行评审的期刊上发表。基因组和表观遗传学数据将在公共开放数据集中提供。 EudraCT号：2012-005655-16； ClinicalTrials.gov 编号：NCT01929616。
Regorafenib was recently approved for patients with pretreated advanced colorectal cancer (aCRC), despite a moderate improvement of the patients’ outcome, and significant toxicities. Based on previous studies showing that early fluorodeoxyglucose-positron emission tomography (FDG-PET)-based metabolic response assessment (MRA) might adequately select patients unlikely to benefit from treatment, the RegARd-C trial uses early MRA to identify likely non-responders to regorafenib in a population of patients with aCRC and guide a comprehensive evaluation of genomic and epigenetic determinants of resistance to treatment. RegARd-C is a multicentric prospective study. Its primary objective is to identify non-benefitters from regorafenib given at 160 mg/day, 3 weeks out of 4 in a population of patients with pretreated aCRC. Baseline PET is repeated at day 14 of the first treatment course. MRA is blinded for the investigators. Overall survival (OS) is the primary end point and will be correlated with metabolic parameters and (epi)genetic alterations assessed from tumour and serial blood samples. A target sample size of 105 evaluable patients (70 as derivation set and 35 as validation set), is considered as sufficient to validate an expected HR for OS of metabolic responders compared to metabolic non-responders significantly <1 (with 80% power and 1-sided 5% α in case of a true HR≤0.59 and a responders rate of 47%). The study was approved by the Institut Jules Bordet's competent ethics committee and complies with the Helsinki declaration or the Belgian laws and regulations, whichever provides the greatest protection for the patient, and follows the International Conference on Harmonisation E 6 (R1) Guideline for Good Clinical Practice, reference number CPMP/ICH/135/95. The protocol and the trials results, even inconclusive, will be presented at international oncology congresses, and published in peer-reviewed journals. Genomic and epigenetic data will be made available in public open data sets. EudraCT number: 2012-005655-16; ClinicalTrials.gov number: NCT01929616.
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影响因子：
8.8
作者：
Strumberg D;Scheulen ME;Schultheis B;Richly H;Frost A;Büchert M;Christensen O;Jeffers M;Heinig R;Boix O;Mross K
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