OMIT Trial: Omitting Therapeutic Lymph Node Dissection in Patients With Stage IIIB/C Melanoma and Major Pathological Response in the Index Lymph Node After Neoadjudvant Immunotherapy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 213
- 试验地点
- 1
- 主要终点
- Local Recurrence Free Survival (LRFS)
研究概览
简要总结
Rationale: The randomized trial NADINA has demonstrated that neoadjuvant treatment with nivolumab with ipilimumab improves event-free survival (EFS) in patients with macroscopic resectable stage III melanoma. In this study, therapeutic lymph node dissection (TLND) was standard of care, showing that patients achieving a major pathological response (MPR, i.e., ≤10% residual viable tumor bed) have an excellent outcome (EFS and Distant Metastasis Free Survival (DMFS)). The PRADO trial indicated that the MPR definition can also be revealed from a surrogate lymph node response, the index lymph node (ILN), allowing sparing the extensive surgery in MPR patients. In these MPR patients the DMFS was 100% after 1 year and 98% after 2 years, and recurrence-free survival (RFS) was 95% after 1 year and 93% after 2 years. Given that TLND is associated with morbidity and has a significant impact on health-related quality of life (HR-QoL) and healthcare costs, this study aims to prospectively investigate the safety of omitting TLND in patients who have an MPR within the ILN after neoadjuvant immunotherapy.
Objectives: To investigate whether TLND can be safely omitted in patients with macroscopic resectable stage III (B/C/D) melanoma achieving an MPR within the ILN upon neoadjuvant treatment with immune checkpoint inhibitors (ipilimumab and nivolumab).
Study design: This study is a prospective, single-arm phase 2 nationwide multicenter trial.
Study population:
Inclusion criteria for study participants are as follows:
- Patients must be eligible for neoadjuvant treatment
- Patients must have a histologically confirmed diagnosis of macroscopic resectable stage III melanoma (stage III B/C/D) with one or more macroscopic lymph node metastasis
- The patient must have a measurable tumor burden that qualifies (according to clinical practice) for neoadjuvant therapy
Intervention: Omitting TLND in patients who achieve an MPR in the ILN following neoadjuvant ipilimumab and nivolumab.
Main study endpoints: The two coprimary endpoints are 2-year Local Recurrence Free Survival (LRFS) and 2-year DMFS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be eligible for neoadjuvant treatment (ipilimumab and nivolumab)
- •Patients must be 16 years of age or older.
- •Patients must have a histologically confirmed diagnosis of macroscopic resectable stage III melanoma (stage III B/C/D) with one or more macroscopic lymph node metastase defined as either one:
- •a palpable node, confirmed as melanoma by pathology; a non-palpable but enlarged lymph node according to RECISTv1.1 (at least 15 mm in short axis), confirmed as melanoma by pathology;
- •a PET scan positive lymph node of any size confirmed as melanoma by pathology;
- •The patient must have a measurable tumor burden that qualifies (according to clinical practice) for neoadjuvant therapy with immune checkpoint inhibitors
- •Patients in whom ILN marking is feasible
- •Written informed consent
排除标准
- •Uveal/ocular or mucosal melanoma
- •WHO performance status of two or more
- •In-transit metastases only (without cytological or histological proven lymph node involvement)
- •Prior targeted therapy targeting BRAF and/or MEK for melanoma
- •Prior immunotherapy targeting CTLA-4, PD-1 or PD-L1 for melanoma
- •Patients with (history of) distant metastasis (stage IV melanoma)
研究组 & 干预措施
Omitting TLND
Omitting TLND in patients who achieve an MPR in the ILN following neoadjuvant ipilimumab and nivolumab.
干预措施: Omitting TLND (Procedure)
Omitting TLND
Omitting TLND in patients who achieve an MPR in the ILN following neoadjuvant ipilimumab and nivolumab.
干预措施: Index node procedure (Procedure)
结局指标
主要结局
Local Recurrence Free Survival (LRFS)
时间窗: 2 years after inclusion
LRFS, as defined as time from removal of the index lymph node (ILN) until local (in basin) recurrence in the MPR group. Accepting a local relapse of 20%.
Distant Metastasis Free Survival (DMFS)
时间窗: 2 years after inclusion
DMFS assessed in the MPR group, as defined as time from the start of neoadjuvant immunotherapy, nivolumab with ipilimumab, until the first occurrence of distant metastasis. Accepting DMFS 3% lower than the 2 years DMFS of the NADINA trial
次要结局
- Evaluation of health-related quality of life (HRQoL), EORTC QLQ C30(3 years after inclusion)
- Evaluation of health-related quality of life (HRQoL), FACT-M(3 years after inclusion)
- Description of the pathological response rates in the ILN(1 year after inclusion)
- Evaluation of the surgical morbidity, CTCAE v5(2 year after inclusion)
- Evaluation of the surgical morbidity, Clavien Dindo(2 year after inclusion)
- Radiological evaluation of the index lymph node(1 year after inclusion)
- Proportion of patients undergoing therapeutic lymph node dissection (TLND)(5 years after inclusion)
- Melanoma specific survival(5 years after inclusion)
- Overall survival(5 years after inclusion)
研究者
D.J. (Dirk) Grünhagen
Associate professor
Erasmus Medical Center