Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy
Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy.
BMJ Open. 2020 Jul 19;10(7):e034393. doi: 10.1136/bmjopen-2019-034393.
Patients with metastatic or locally advanced, non-resectable, grade 3 poorly differentiated gastroenteropancreatic (GEP) and lung neuroendocrine carcinomas (NECs) are usually treated with in first-line platinum compounds. There is no standard second-line treatment on progression. Accurate biomarkers are needed to facilitate diagnosis and prognostic assessment of patients with NEC.
The SEcond-line therapy in NEuroendocrine CArcinomas (SENECA) study is a randomised, non-comparative, multicentre phase II trial designed to evaluate the efficacy and safety of folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) or capecitabine plus temozolomide (CAPTEM) regimens after failure of first-line chemotherapy in patients with lung NEC and GEP-NEC. Secondary aims are to correlate the serum miRNA profile and primary mutational status of MEN1, DAXX, ATRX and RB-1 with prognosis and outcome and to investigate the prognostic and predictive role of the Ki-67 score and 18-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) or Ga-PET/CT. The main eligibility criteria are age ≥18 years; metastatic or locally advanced, non-resectable, grade 3 lung or GEP-NECs; progression to first-line platinum-based chemotherapy. A Bryant and Day design taking into account treatment activity and toxicity was used to estimate the sample size. All analyses will be performed separately for each treatment group in the intention-to-treat population. A total of 112 patients (56/arm) will be randomly assigned (1:1) to receive FOLFIRI every 14 days or CAPTEM every 28 days until disease progression or unacceptable toxicity or for a maximum of 6 months. Patients undergo testing for specific biomarkers in primary tumour tissue and for miRNA in blood samples. MiRNA profiling will be performed in the first 20 patients who agree to participate in the biological substudy.
The SENECA trial, supported by Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), was authorised by the locals Ethics Committee and the Italian Medicines Agency (AIFA). Results will be widely disseminated via peer-reviewed manuscripts, conference presentations and reports to relevant authorities.The study is currently open in Italy.
NCT03387592; Pre-results. EudraCT-2016-000767-17.
Clinical Study Protocol Version 1, 7 November 2016.
转移性或局部晚期、不可切除、3 级低分化胃肠胰（GEP）和肺神经内分泌癌（NEC）患者通常采用一线铂类化合物治疗。在疾病进展时，尚无标准的二线治疗方法。需要准确的生物标志物来促进 NEC 患者的诊断和预后评估。
SEcond-line therapy in NEuroendocrine CArcinomas（SENECA）研究是一项随机、非对照、多中心 II 期试验，旨在评估在一线化疗失败后，患者接受亚叶酸、5-氟尿嘧啶和伊立替康（FOLFIRI）或卡培他滨联合替莫唑胺（CAPTEM）方案治疗肺 NEC 和 GEP-NEC 的疗效和安全性。次要目标是将血清 miRNA 谱和 MEN1、DAXX、ATRX 和 RB-1 的主要突变状态与预后和结果相关联，并研究 Ki-67 评分和 18-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描（F-FDG PET/CT）或 Ga-PET/CT 的预后和预测作用。主要入选标准为年龄≥18 岁；转移性或局部晚期、不可切除、3 级肺或 GEP-NEC；进展至一线铂类化疗。采用考虑治疗活性和毒性的 Bryant 和 Day 设计来估计样本量。所有分析均将在意向治疗人群中分别针对每个治疗组进行。共 112 名患者（每组 56 名）将被随机分配（1:1）接受每 14 天一次的 FOLFIRI 或每 28 天一次的 CAPTEM，直至疾病进展或不可耐受的毒性或最长 6 个月。患者在原发性肿瘤组织中进行特定生物标志物检测，并在血液样本中进行 miRNA 检测。同意参与生物学子研究的前 20 名患者将进行 miRNA 谱分析。
由 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori（IRST）支持的 SENECA 试验，已获得当地伦理委员会和意大利药品管理局（AIFA）的授权。结果将通过同行评议的论文、会议演讲和向相关当局的报告广泛传播。该研究目前在意大利开放。
NCT03387592；预结果。EudraCT-2016-000767-17。
临床研究方案版本 1，2016 年 11 月 7 日。
