一项关于长疗程新辅助放化疗联合替雷利珠单抗随后行全直肠系膜切除术治疗局部晚期直肠癌安全性和疗效评估的前瞻性、多中心、II期临床试验的原理与设计（NCRT-PD1-LARC试验）
Rationale and design of a prospective, multicenter, phase II clinical trial of safety and efficacy evaluation of long course neoadjuvant chemoradiotherapy plus tislelizumab followed by total mesorectal excision for locally advanced rectal cancer (NCRT-PD1-LARC trial).
作者信息
Yang Zhengyang, Zhang Xiao, Zhang Jie, Gao Jiale, Bai Zhigang, Deng Wei, Chen Guangyong, An Yongbo, Liu Yishan, Wei Qi, Han Jiagang, Li Ang, Liu Gang, Sun Yi, Kong Dalu, Yao Hongwei, Zhang Zhongtao
机构信息
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China.
Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
出版信息
BMC Cancer. 2022 Apr 27;22(1):462. doi: 10.1186/s12885-022-09554-9.
BACKGROUND
Long course radiotherapy plus neoadjuvant chemotherapy followed by resection (total mesorectal excision, TME) has accepted widespread recognized in the treatment of locally advanced rectal cancer (LARC). Tislelizumab, an anti-PD1 humanized IgG4 monoclonal antibody, has been demonstrated with clinical activity and is approved for treating recurrent/refractory classical Hodgkin lymphoma and locally advanced/metastatic urothelial carcinoma in China. However, the safety and efficacy of long course (neoadjuvant chemoradiotherapy, NCRT) plus tislelizumab followed by TME for LARC is still uncertain.
METHODS
This NCRT-PD1-LARC trial will be a prospective, multicenter and phase II clinical trial designed to evaluate the safety and efficacy of LARC patients treated with long course NCRT plus tislelizumab followed by TME. This trial will consecutively enroll 50 stage II/III LARC patients (cT3N0M0 and cT1-3N1-2M0) with the tumor distal location ≤ 7 cm from anal verge at 7 centers in China. The enrolled patients will receive long course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day8), followed by TME 6-8 weeks after the end of radiotherapy. The primary efficacy endpoint will be the pathological complete response (pCR) rate, which is defined as absence of viable tumor cells in the primary tumor and lymph nodes.
DISCUSSION
To our knowledge, this trial is the first multicenter clinical trial in China to assess the safety and efficacy of NCRT plus anti-PD1 therapy followed by TME to treat patients with LARC. NCRT followed by TME was recognized as the most recommended treatment against LARC while could not be completely satisfied in clinic. This study expects to provide a solid basis and encouraging outcomes for this promising combination of radiotherapy, chemotherapy and immunotherapy in LARC.
TRIAL REGISTRATION
Name of the registry: ClinicalTrials.gov.
TRIAL REGISTRATION NUMBER
NCT04911517. Date of registration: 23 May 2021. URL of trial registry record: https://www.
CLINICALTRIALS
gov/ct2/show/NCT04911517?id=BFH-NCRTPD&draw=2&rank=1 .
背景
长程放疗联合新辅助化疗后行切除术（全直肠系膜切除术，TME）在局部晚期直肠癌（LARC）的治疗中已得到广泛认可。替雷利珠单抗是一种抗PD1人源化IgG4单克隆抗体，已显示出临床活性，并在中国被批准用于治疗复发/难治性经典霍奇金淋巴瘤以及局部晚期/转移性尿路上皮癌。然而，长程（新辅助放化疗，NCRT）联合替雷利珠单抗后行TME治疗LARC的安全性和疗效仍不确定。
方法
这项NCRT-PD1-LARC试验将是一项前瞻性、多中心的II期临床试验，旨在评估长程NCRT联合替雷利珠单抗后行TME治疗LARC患者的安全性和疗效。该试验将在中国的7个中心连续招募50例II/III期LARC患者（cT3N0M0和cT1-3N1-2M0），肿瘤远端位置距肛缘≤7 cm。入组患者将接受长程放疗（50 Gy/25次，2 Gy/次，每周5天）以及三个21天周期的卡培他滨（1000 mg/m²，每日两次，口服，第1 - 14天）加三个21天周期的替雷利珠单抗（200 mg，静脉滴注，第8天），放疗结束后6 - 8周行TME。主要疗效终点将是病理完全缓解（pCR）率，定义为原发肿瘤和淋巴结中无存活肿瘤细胞。
讨论
据我们所知，本试验是中国首个评估NCRT联合抗PD1治疗后行TME治疗LARC患者安全性和疗效的多中心临床试验。NCRT后行TME被认为是治疗LARC最推荐的方法，但在临床中仍不能完全令人满意。本研究期望为这种放疗、化疗和免疫治疗在LARC中的有前景的联合应用提供坚实的基础和令人鼓舞的结果。
试验注册
注册机构名称：ClinicalTrials.gov。
试验注册号
NCT04911517。注册日期：2021年5月23日。试验注册记录的网址：https://www.
CLINICALTRIALS
gov/ct2/show/NCT04911517?id=BFH-NCRTPD&draw=2&rank=1 。
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