Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands.
Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands.
BMC Cancer. 2022 Sep 6;22(1):957. doi: 10.1186/s12885-022-09947-w.
The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients.
This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life.
This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis.
Clinicaltrials.gov: NCT04838496 , registered on 02-04-2021 Netherlands Trial Register: NL9790.
Version 3 dd 11-4-2022.
直肠系膜筋膜（MRF）侵犯、4 级外膜静脉侵犯（EMVI）、肿瘤沉积（TD）或 MRI 上广泛或双侧直肠旁（外侧）淋巴结（LLN）肿大，这些特征提示存在明确的、广泛局部晚期直肠癌（LARC），这些患者具有较高的治疗失败风险。本研究旨在评估新辅助放化疗前强化化疗是否能提高这些患者的完全缓解（CR）率。
这是一项多中心、单臂、开放标签、Ⅱ期临床试验，将纳入 128 例非转移性高危局部晚期直肠癌（hr-LARC）患者，适合三联化疗。为了确保研究人群具有明确的、不利的预后特征，hr-LARC 定义为基线 MRI 至少有以下一种特征的 LARC：MRF 侵犯、EMVI 4 级、双侧或广泛 LLN 肿大，有不完全切除的高危因素，或 TD。排除标准为存在纯合型 DPD 缺乏、远处转移、过去 6 个月内接受任何化疗、盆腔区域既往放疗导致无法行标准放化疗，以及计划治疗的任何禁忌症。所有患者在接受放化疗（25×2 Gy 或 28×1.8 Gy 同期卡培他滨）前，均计划接受六周期两周一次的 FOLFOXIRI（5-氟尿嘧啶、亚叶酸、奥沙利铂和伊立替康）。在放化疗完成后，如影像学证实可切除疾病，将进行手术切除。如果临床完全缓解，可采用观察等待策略。主要终点是 CR 率，定义为病理 CR 或放化疗后 1 年持续临床 CR。主要次要终点是长期肿瘤学结局、影像学和病理学反应、切缘清晰的切除数量、治疗相关毒性、围手术期并发症、健康相关成本和生活质量。
本试验方案描述了 MEND-IT 研究。MEND-IT 研究旨在评估在一组局部晚期直肠癌患者中，在放化疗前进行强化化疗对明确的、不利特征（定义为 hr-LARC）的患者的 CR 率的影响，以改善其预后。
Clinicaltrials.gov：NCT04838496，注册于 2021 年 4 月 2 日；荷兰临床试验注册中心：NL9790。
第 3 版，2022 年 4 月 11 日。
