Molecular Outcome Prediction of Neoadjuvant Systemic Treatment in Esophagogastric Carcinoma
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Aim 1: Correlation of in-vitro response in the organoid model with histological regression in the resected tumor
研究概览
简要总结
Patients with locally advanced, resectable gastric or esophagogastric junction adenocarcinoma will receive a biopsy of the primary tumor, followed by standard-of care neoadjuvant systemic treatment; after neoadjuvant therapy tumor biopsies will be taken from different sites of the resection specimen.
- Aim 1: Organoid cultures of pre-treatment tumor biopsies will be established and exposed to the same chemotherapy as the corresponding patient; in vitro response to treatment will be correlated with the in vivo response of patients.
- Aim 2: Whole genome, methylome and RNA sequencing of tumors biopsies and organoids will be performed prior to as well as after systemic treatment. Histological and clinical outcome will be correlated with molecular subtypes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed, resectable adenocarcinoma of the GEJ (type I-III) or the stomach (cT2, cT3,cT4, any cN category, M0), or any cT cN+ M0 with the following specifications:
- •ECOG-Score ≤ 2
- •Patient is fit to undergo surgery (either subtotal or total gastrectomy, transhiatal or abdominothoracic esophagectomy)
- •No preceding cytotoxic or targeted therapy
- •No prior partial or complete tumor resection
- •Exclusion of distant metastasis by CT or MRI of thorax and abdomen, and optionally bone scan (if osseous lesions are suspected due to clinical signs)
排除标准
- •Patients with distant metastasis
- •Known hypersensitivity against components of the neoadjuvant systemic treatment
- •Documented history of congestive heart failure NYHA ≥III, myocardial infarction within the past 3 months before the start of neoadjuvant treatment
- •Uncontrollable high-risk cardiac arrhythmia, e.g. significant ventricular arrhythmia
- •Past or current history of other malignancies not curatively treated and without evidence of disease for more than 5 years, except for curatively treated early stage cancers such as basal cell carcinoma of the skin and in situ carcinoma of the cervix or the bladder.
结局指标
主要结局
Aim 1: Correlation of in-vitro response in the organoid model with histological regression in the resected tumor
时间窗: 1 year
Correlation of in-vitro response to cytotoxic chemotherapy in the patient-derived organoid model with histological regression in the resected specimen and analysis of reliability of this organoid model in predicting patients' response to neoadjuvant chemotherapy.
Aim 2: Correlation of molecular subtypes with histological response after neoadjuvant therapy in patients
时间窗: 1 year
Prognostic impact of the molecular subtypes on histological response to neoadjuvant chemotherapy in patients will be modeled using the logistic regression.
次要结局
- Aim 1: Correlation of in-vitro response in the organoid model with relapse-free survival(maximum 5 years)
- Aim 2: Correlation of molecular subtypes with relapse-free survival(maximum 5 years)
研究者
Georg Martin Haag
NCT, Dep. Medical Oncology
University Hospital Heidelberg