研究方案：一项多中心随机研究，对局部晚期胰腺癌（SCALOP-2）进行诱导化疗后联合卡培他滨±奈非那韦，加或不加高剂量或标准剂量放疗。
Study protocol: a multi-centre randomised study of induction chemotherapy followed by capecitabine ± nelfinavir with high- or standard-dose radiotherapy for locally advanced pancreatic cancer (SCALOP-2).
机构信息
Centre for Statistics in Medicine, University of Oxford, Oxford, UK.
Oncology Clinical Trials Office, University of Oxford, Oxford, UK.
出版信息
BMC Cancer. 2019 Feb 4;19(1):121. doi: 10.1186/s12885-019-5307-z.
BACKGROUND
Induction chemotherapy followed by chemoradiation is a treatment option for patients with locally advanced pancreatic cancer (LAPC). However, overall survival is comparable to chemotherapy alone and local progression occurs in nearly half of all patients, suggesting chemoradiation strategies should be optimised. SCALOP-2 is a randomised phase II trial testing the role of radiotherapy dose escalation and/or the addition of the radiosensitiser nelfinavir, following induction chemotherapy of gemcitabine and nab-paclitaxel (GEMABX). A safety run-in phase (stage 1) established the nelfinavir dose to administer with chemoradiation in the randomised phase (stage 2).
METHODS
Patients with locally advanced, inoperable, non-metastatic pancreatic adenocarcinoma receive three cycles of induction GEMABX chemotherapy prior to radiological assessment. Those with stable/responding disease are eligible for further trial treatment. In Stage 1, participants received one further cycle of GEMABX followed by capecitabine-chemoradiation with escalating doses of nelfinavir in a rolling-six design. Stage 2 aims to register 262 and randomise 170 patients with responding/stable disease to one of five arms: capecitabine with high- (arms C + D) or standard-dose (arms A + B) radiotherapy with (arms A + C) or without (arms B + D) nelfinavir, or three more cycles of GEMABX (arm E). Participants allocated to the chemoradiation arms receive another cycle of GEMABX before chemoradiation begins. Co-primary outcomes are 12-month overall survival (radiotherapy dose-escalation question) and progression-free survival (nelfinavir question). Secondary outcomes include toxicity, quality of life, disease response rate, resection rate, treatment compliance, and CA19-9 response. SCALOP-2 incorporates a detailed radiotherapy quality assurance programme.
DISCUSSION
SCALOP-2 aims to optimise chemoradiation in LAPC and incorporates a modern induction regimen.
TRIAL REGISTRATION
Eudract No: 2013-004968-56; ClinicalTrials.gov : NCT02024009.
背景
诱导化疗后联合放化疗是局部晚期胰腺癌（LAPC）患者的一种治疗选择。然而，总生存期与单独化疗相当，近一半的患者发生局部进展，这表明放化疗策略应得到优化。SCALOP-2 是一项随机 II 期试验，旨在检验在吉西他滨和 nab-紫杉醇（GEMABX）诱导化疗后，放疗剂量递增和/或添加放射增敏剂奈非那韦在局部晚期不可切除、无转移胰腺腺癌中的作用。一个安全的入组阶段（第 1 阶段）确定了在随机阶段（第 2 阶段）中与放化疗联合使用的奈非那韦剂量。
方法
局部晚期、不可切除、无转移的胰腺腺癌患者在影像学评估前接受三个周期的诱导 GEMABX 化疗。那些疾病稳定/有反应的患者有资格进一步接受试验治疗。在第 1 阶段，参与者接受了一个额外的 GEMABX 周期，然后在滚动 6 设计中接受卡培他滨-放化疗，奈非那韦剂量递增。第 2 阶段的目标是注册 262 名并随机分配 170 名有反应/稳定疾病的患者至五个治疗组之一：卡培他滨联合高剂量（C+D 臂）或标准剂量（A+B 臂）放疗，伴有（A+C 臂）或不伴有（B+D 臂）奈非那韦，或再接受三个周期的 GEMABX（E 臂）。分配至放化疗组的患者在开始放化疗前再接受一个 GEMABX 周期。主要终点是 12 个月总生存率（放疗剂量递增问题）和无进展生存率（奈非那韦问题）。次要终点包括毒性、生活质量、疾病缓解率、切除率、治疗依从性和 CA19-9 反应。SCALOP-2 纳入了详细的放疗质量保证计划。
讨论
SCALOP-2 旨在优化局部晚期胰腺癌的放化疗，并纳入了一种现代诱导方案。
试验注册
Eudract No：2013-004968-56；ClinicalTrials.gov：NCT02024009。
Zotero 插件