EFFORT 研究方案：在不可切除/转移性结直肠癌患者中，FOLFOXIRI 联合贝伐珠单抗治疗进展后或维持治疗期间使用 FOLFIRI 联合阿柏西普二线治疗的前瞻性研究。
Protocol of the EFFORT study: a prospective study of FOLFIRI plus aflibercept as second-line treatment after progression on FOLFOXIRI plus bevacizumab or during maintenance treatment in patients with unresectable/metastatic colorectal cancer.
机构信息
Cancer Treatment Center, Kansai Medical University Hospital, Hirakata, 573-1191, Japan.
Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, 812-8582, Japan.
出版信息
BMC Cancer. 2020 Nov 17;20(1):1116. doi: 10.1186/s12885-020-07576-9.
BACKGROUND
FOLFOXIRI plus bevacizumab is used as a first-line therapy for patients with unresectable or metastatic colorectal cancer. However, there are no clear recommendations for second-line therapy after FOLFOXIRI plus bevacizumab combination. Here, we describe our planning for the EFFORT study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC.
METHODS
EFFORT is an open-label, multicenter, single arm phase II study to evaluate whether a FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Patients with unresectable or metastatic colorectal cancer who received FOLFOXIRI plus bevacizumab as a first-line therapy will receive aflibercept and FOLFIRI (aflibercept 4 mg/kg, irinotecan 150 mg/m IV over 90 min, with levofolinate 200 mg/m IV over 2 h, followed by fluorouracil 400 mg/m bolus and fluorouracil 2400 mg/m continuous infusion over 46 h) every 2 weeks on day 1 of each cycle. The primary endpoint is progression-free survival (PFS). To achieve 80% power to show a significant response benefit with a one-sided alpha level of 0.10, assuming a threshold progression-free survival of 3 months and an expected value of at least 5.4 months, we estimated that 32 patients are necessary. Secondary endpoints include overall survival, overall response rate, safety, and exploratory biomarker analysis for differentiating anti-VEGF drug in 2nd-line chemotherapy for unresectable or metastatic colorectal cancer.
DISCUSSION
This is the first study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for unresectable or metastatic colorectal cancer. Switching to a different type of anti-VEGF drug in second-line therapy after FOLFOXIRI plus bevacizumab appears to be an attractive treatment strategy when considering survival benefit. It is expected that this phase II study will prove the efficacy of this strategy and that a biomarker for drug selection will be discovered.
TRIAL REGISTRATION
Japan Registry of Clinical Trials jRCTs071190003 . Registered April 18, 2019.
背景
FOLFOXIRI 联合贝伐珠单抗被用作不可切除或转移性结直肠癌患者的一线治疗。然而，对于 FOLFOXIRI 联合贝伐珠单抗治疗后，尚无明确的二线治疗推荐。在这里，我们描述了我们对 EFFORT 研究的计划，以研究 FOLFOXIRI 联合贝伐珠单抗治疗 mCRC 后，FOLFIRI 联合阿柏西普是否具有疗效。
方法
EFFORT 是一项开放标签、多中心、单臂 II 期研究，旨在评估 FOLFOXIRI 联合贝伐珠单抗治疗 mCRC 后，FOLFIRI 联合阿柏西普是否具有疗效。接受 FOLFOXIRI 联合贝伐珠单抗作为一线治疗的不可切除或转移性结直肠癌患者将接受阿柏西普和 FOLFIRI（阿柏西普 4mg/kg，伊立替康 150mg/m 静脉输注 90 分钟，左亚叶酸 200mg/m 静脉输注 2 小时，随后氟尿嘧啶 400mg/m 推注，氟尿嘧啶 2400mg/m 持续输注 46 小时）每 2 周 1 天 1 周期。主要终点是无进展生存期（PFS）。为了以单侧 α 水平 0.10 达到 80%的功效，假设无进展生存期阈值为 3 个月，预期值至少为 5.4 个月，我们估计需要 32 例患者。次要终点包括总生存期、总缓解率、安全性和探索性生物标志物分析，以区分不可切除或转移性结直肠癌二线化疗中的抗 VEGF 药物。
讨论
这是第一项研究，旨在研究 FOLFOXIRI 联合贝伐珠单抗治疗不可切除或转移性结直肠癌后，FOLFIRI 联合阿柏西普是否具有疗效。考虑到生存获益，在 FOLFOXIRI 联合贝伐珠单抗治疗后二线治疗中改用不同类型的抗 VEGF 药物似乎是一种有吸引力的治疗策略。预计这项 II 期研究将证明该策略的疗效，并发现药物选择的生物标志物。
试验注册
日本临床试验注册中心 jRCTs071190003。注册于 2019 年 4 月 18 日。
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