2025-521158-40-00招募中2 期
Total Neoadjuvant Therapy for lymph node-positive adenocarcinoma of the OESophagus and oesophagogastric junction: TNT-OES-2 trial
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)12 个研究点 分布在 1 个国家目标入组 12 人开始时间: 2025年8月4日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 12
- 主要终点
- • The progression-free survival defined as the time interval from randomization to the first event of local failure, regional failure, progression to metastatic disease or death
研究概览
简要总结
• To determine the progression-free survival at 2 years after TNT (either TNT FLOT-CROSS and TNT CROSS-FLOT combination)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Patients with cT2-4aN+M0 resectable adenocarcinoma of the oesophagus or EGJ (Siewert type I-II) according to the 8th edition of the Union for International Cancer Control (UICC) TNM classification for Esophageal Cancer who are planned to undergo nCRT or FLOT (43). In case of stage cT4a, curative resectability has to be explicitly verified by the multidisciplinary tumor board. Clinical N+ status should be determined by EUS or 18F-FDG PET/CT.
- •Adequate cardiac and respiratory function (cardiac or pulmonary function tests such only necessary in symptomatic patients).
- •Adequate bone marrow function (White Blood Cells >3x109/L; Haemoglobin >5.5 mmol/L; platelets >100x109/L). In the event of transfusions, the last red blood cell transfusion should be more than 2 weeks before inclusion.
- •Adequate renal function (Glomerular Filtration Rate >50 ml/min) or serum creatinine ≤1.5 x upper limit of normal (ULN) and adequate liver function (total bilirubin <1.5x Upper Level of Normal (ULN); Aspartate transaminase (AST) <2.5x ULN and Alanine transaminase (ALT) <3x ULN.
- •A negative serum pregnancy test in women of child-bearing potential during screening period.
- •Use of adequate contraception during the study up to 3 months after the end of the study.
- •Written informed consent and ability to understand the nature of the study and the study-related procedures and to comply with them.
- •Maximum of 4 cm ingrowth in the cardia, measured by upper endoscopy.
- •In case of tumor and/or lymph node involvement below the diaphragm, the most proximal involved lymph node station cannot be higher than N7 (Appendix C).
- •In case of no tumor or lymph node involvement below the diaphragm, the most proximal involved lymph node station cannot be higher than N4 (Appendix C).
- •Age ≥ 18 years. For patients aged 70 years or older, a geriatric screening tool (G8) should be used to assess functioning across the domains. If a patient has a score of 14 or lower on the G8, a comprehensive geriatric assessment (CGA) should be done prior to inclusion (Appendix D).
- •No prior abdominal, thoracic or cervical radiotherapy overlapping with the CROSS irradiation fields.
- •No prior cytotoxic chemotherapy for oesophageal cancer.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 (44).
- •Weight loss <10%.
排除标准
- •Patients with tumours of squamous, adenosquamous or other non-adenocarcinoma histology.
- •Language difficulty, dementia or altered mental status prohibiting the understanding and giving of informed consent and to complete quality of life questionnaires.
- •Patients who are eligible for and want to participate in the TRAP-2 trial (NCT05188313)
- •Patients with overt hematogenous (organ) metastasis, distant lymphatic metastases (cervical/retroperitoneal), peritoneal or pleural dissemination, as detected on 18F-FDG PET/CT or regular CT-scan. In patients in whom a diagnostic laparoscopy is indicated (to assess resectability or to exclude peritoneal disease), tumor-positive cytology peritoneal fluid is also an exclusion criteria.
- •Clinically significant (active) cardiac disease (e.g. symptomatic coronary artery disease of myocardial infarction within the last 12 months) or lung disease (forced expiratory volume in one second (FEV1) <1.5L).
- •Peripheral neuropathy grade >1, according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (37).
- •Homozygous DPYD genotype (tested for *2A, *13, 2846A>T, and 1236G>A)
- •Pregnant and lactating women, or patients of reproductive potential who are not using effective contraception. If barrier contraceptives are used, they must be continued by both sexes throughout the study.
- •Other active malignancies with a prognosis interfering with that of oesophageal cancer.
- •Expected lack of compliance with the protocol.
结局指标
主要结局
• The progression-free survival defined as the time interval from randomization to the first event of local failure, regional failure, progression to metastatic disease or death
• The progression-free survival defined as the time interval from randomization to the first event of local failure, regional failure, progression to metastatic disease or death
次要结局
- • Feasibility is defined as the proportion of patients that complete all 4 cycles of FLOT and all 5 chemotherapy cycles of CROSS, permitting dose reductions and delays
- • Overall survival (OS), calculated from the date of randomization to the date of death due to any cause or, for patients alive at trial closure, date of last follow-up
- • The number of patients with any major systemic therapy related toxicity, defined as grade ≥ 3 according to the Common Terminology Criteria for Adverse Events (CTCAE ) version 5.0), up to one month after the last administration of TNT (37)
- • The rate of any grade mucositis, up to one month after the last administration of TNT
- • The number of patients requiring dose reductions or treatment delays during CROSS and FLOT
- • The number of patients requiring G-CSF as primary or secondary prophylaxis
- • The number of serious adverse events (SAEs), up to one month after last administration of TNT
- • Surgical morbidity (Clavien-Dindo ≥3) and mortality (30-day, 90-day and/or in-hospital mortality), monitored within the Dutch upper gastrointestinal cancer audit (DUCA) surgical complications registry (38)
- • The proportion of resections that are radical (R0), microscopically irradical (R1) and macroscopically irradical (R2)
- • The proportion of patients that is unable to undergo oesophagectomy due to clinical deterioration
- • The proportion of patients that choose for an active surveillance strategy instead of surgery after CRE-2
- • Clinical complete response (cCR) rate is defined as the percentage of patients without residual locoregional disease or distant metastases at CRE-2
- • Pathological complete response (pCR) rate in those who underwent an oesophagectomy is defined as ypT0N0
- • Major pathological response in those who underwent oesophagectomy, defined as Mandard 1-2 (39)
- • The distant dissemination rate, defined as the proportion of metastases at 12 weeks after completion of TNT FLOT-CROSS or TNT CROSS-FLOT, detected by 18F-FDG
- • Health-related quality of life (HRQoL), as measured by QoL questionnaires: EORTC QLQ-OG25 and EORTC-C30 (40, 41)
研究者
E.A. de Bruijn
Scientific
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
研究点 (12)
Loading locations...
相似试验
招募中
2 期
Safety and Efficacy of Neoadjuvant immunotherapy with Durvalumab (MEDI 4736) in combination with neoadjuvant chemotherapy (Gemcitabin/Cisplatin or Gemcitabin/Carboplatin) in patients with operable, high-risk, localized urothelial carcinoma of the upper urinary tract. iNDUCT - GETUG V082024-516077-72-02Centre Hospitalier Universitaire De Nimes50
招募中
3 期
Efficacy and safety of conventional neoadjuvant therapy versus total neoadjuvant therapy in older patients with locally advanced rectal cancer: a multicentre, open-label, randomised pragmatic clinical trial2023-506703-26-00Institut Jules Bordet264
招募中
2 期
Neoadjuvant Lu-PSMA radioligand therapy and Ipilimumab in men with very high-risk prostate cancer (NEPI)2024-514386-19-00Universitaetsklinikum Essen AöR58
招募中
不适用
Response-adapted Total Neoadjuvant Therapy Guided by Induction Chemotherapy in Early- and Intermediate-risk Low Rectal Cancer for Implementation of a Watch-and-wait StrategyNCT07260526West China Hospital60
招募中
2 期
Study of chemotherapy and immunotherapy for patients with lung cancer bounded in the thorax and potentially resectable2024-513731-24-00Fundacion GECP90