TRICOLORE试验的研究方案：一项关于奥沙利铂为基础的化疗与S-1、伊立替康和贝伐单抗联合化疗作为转移性结直肠癌一线治疗的随机III期研究。

Study protocol of the TRICOLORE trial: a randomized phase III study of oxaliplatin-based chemotherapy versus combination chemotherapy with S-1, irinotecan, and bevacizumab as first-line therapy for metastatic colorectal cancer.

作者信息

Komatsu Yoshito, Ishioka Chikashi, Shimada Ken, Yamada Yasuhide, Gamoh Makio, Sato Atsushi, Yamaguchi Tatsuro, Yuki Satoshi, Morita Satoshi, Takahashi Shin, Goto Rei, Kurihara Minoru

机构信息

Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Kita-15 Nishi-7 Kita-ku, Sapporo, 060-8638, Japan.

Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.

出版信息

BMC Cancer. 2015 Sep 9;15:626. doi: 10.1186/s12885-015-1630-1.

DOI:10.1186/s12885-015-1630-1

PMID:26353772

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4565014/

Abstract

BACKGROUND

Metastatic colorectal cancer carries a poor prognosis and cannot be cured by currently available therapy. Chemotherapy designed to prolong survival and improve the quality of life (QOL) of patients is the mainstay of treatment. Standard regimens of FOLFOX/bevacizumab and CapeOX/bevacizumab can cause neurotoxicity, potentially disrupting treatment. The results of 3 phase II studies of combination therapy with S-1, irinotecan, and bevacizumab showed comparable efficacy to mFOLFOX6/bevacizumab and CapeOX/bevacizumab, without severe neurotoxicity. Therefore, the establishment and evaluation of S-1-containing irinotecan-based regimens for first-line treatment are expected to become more important.

METHODS

The TRICOLORE trial is a multicenter, randomized, open-label, controlled phase III study which aims to evaluate the non-inferiority of combination therapy with S-1/irinotecan/bevacizumab (a 3-week regimen [SIRB] or 4-week regimen [IRIS/bevacizumab]) to oxaliplatin-based standard treatment (mFOLFOX6/bevacizumab or CapeOX/bevacizumab) in patients with metastatic colorectal cancer who had not previously received chemotherapy. Patients will be randomly assigned to either the control group (mFOLFOX6/bevacizumab or CapeOX/bevacizumab) or study group (SIRB or IRIS/bevacizumab). The target sample size is 450 patients. The primary endpoint is progression-free survival (PFS), and the secondary endpoints are overall survival (OS), response rate (RR), time to treatment failure (TTF), relative dose intensity (RDI), the incidence and severity of adverse events, quality of life (QOL), quality-adjusted life years (QALY), health care costs, and relations between biomarkers and treatment response (translational research, TR).

DISCUSSION

The results of this study will provide important information that will help to improve the therapeutic strategy for metastatic colorectal cancer, and we believe that this study is very meaningful from the perspective of comparative effectiveness research.

TRIAL REGISTRATION

UMIN000007834.

摘要

背景

转移性结直肠癌预后较差，目前可用的治疗方法无法治愈。旨在延长患者生存期并改善生活质量（QOL）的化疗是主要治疗手段。FOLFOX/贝伐单抗和CapeOX/贝伐单抗的标准方案可导致神经毒性，可能会中断治疗。三项关于S-1、伊立替康和贝伐单抗联合治疗的II期研究结果显示，其疗效与mFOLFOX6/贝伐单抗和CapeOX/贝伐单抗相当，且无严重神经毒性。因此，建立并评估含S-1的伊立替康一线治疗方案有望变得更为重要。

方法

TRICOLORE试验是一项多中心、随机、开放标签、对照的III期研究，旨在评估S-1/伊立替康/贝伐单抗联合治疗（3周方案[SIRB]或4周方案[IRIS/贝伐单抗]）对比基于奥沙利铂的标准治疗（mFOLFOX6/贝伐单抗或CapeOX/贝伐单抗）对既往未接受过化疗的转移性结直肠癌患者的非劣效性。患者将被随机分配至对照组（mFOLFOX6/贝伐单抗或CapeOX/贝伐单抗）或研究组（SIRB或IRIS/贝伐单抗）。目标样本量为450例患者。主要终点为无进展生存期（PFS），次要终点为总生存期（OS）、缓解率（RR）、治疗失败时间（TTF）、相对剂量强度（RDI）、不良事件的发生率和严重程度、生活质量（QOL）、质量调整生命年（QALY）、医疗保健成本以及生物标志物与治疗反应之间的关系（转化研究，TR）。