Metabolic and Molecular Response Evaluation for the Individualization of Therapy in Adenocarcinomas of the Gastroesophageal Junction
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- R0 resection rate
研究概览
简要总结
Metabolic and Molecular Response evaluation for the individualization of therapy in adenocarcinomas of the gastroesophageal junction by evaluation of the R0 resection rate for patients with metabolically (ie, according to PET criteria) chemotherapy-resistant locally advanced AEG, who receive an intensified neoadjuvant chemoradiotherapy (INRCT). Additonal efforts will be done by investigation of molecular and metabolic biomarkers in relation to their predictive and prognostic value by correlating them with histopathologic responses and clinical outcome in an exploratory approach.
详细描述
Adenocarcinomas of the esophagus and the esophagogastric junction (AEG) are clinically-topographically divided into subtypes I-III according to the Siewert classification and show an increased incidence. Neoadjuvant and/or perioperative chemotherapy or preoperative radiochemotherapy is well established in the management of AEG. However, a significant number of patients do not respond to preoperative chemotherapy, suffering from toxicity and facing a worse outcome due to lower R0 resection rates. Previous results from the MUNICON-1 and MUNICON-2 trials have shown that PET-based therapy individualization can be successfully integrated in neoadjuvant treatment algorithms.
Tumor-free resection edges (R0) constitute the greatest prognostic advantage in terms of overall survival. However, the R0 resection rates for patients who, according to early metabolic response evaluation, have not responded to the chemotherapy, have not been satisfactory, even after conversion to an - albeit moderate - radiochemotherapy in the MUNICON-2 trial. Thus, this patient population (so-called non responders) so far lack a beneficial neoadjuvant therapy modality.
Based on these results, the primary goal of MEMORI study is to evaluate the R0 resection rate for patients with metabolically (ie, according to PET criteria) chemotherapy-resistant locally advanced AEG, who receive an intensified neoadjuvant chemoradiotherapy (INRCT). Secondary it is planned to investigate molecular and metabolic biomarkers in relation to their predictive and prognostic value by correlating them with histopathologic responses and clinical outcome in an exploratory approach.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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 AEG I-III
- •Potentially R0 - resectable AEG and primary tumor category UT2 -4
- •Functional operability : Exclusion of OP - limiting comorbidities
- •Intense FDG tracer uptake of the tumor during Baseline PET/CT examination and thus suitability for monitoring and early response prediction by FDG - PET ( [ 18F ] - FDG uptake in the tumor at baseline > 1.35 x liver SUV + 2 x standard deviation of the liver SUV)
- •Performance status (ECOG ) 0 or 1
- •Age : ≥ 18
- •creatinine clearance > 60ml/min measured in a 24 h urine or calculated with the Cockgroft -Gault formula
- •bilirubin ≤ 1.5 times upper limit of normal , serum transaminases (GOT
- •/ GPT ) ≤ 3 times ULN
- •leukocytes ≥ 3.5 g / l, platelet ≥ 100 g / l
- •Negative pregnancy test (determination of beta- HCG in urine or serum) in women of childbearing potential
- •A signed consent form after implementation of medical education
排除标准
- •Existing distant metastases (M1b)
- •Tumor infiltration into the tracheobronchial system
- •Previous radiotherapy targeted at the thorax
- •Lack of ability of the patient to adhere to the protocol rules
- •Manifest heart failure despite optimal medication> NYHA I
- •existing angina pectoris at rest or undergoing stress without clarification via interventional cardiology and / or myocardial infarction within the last 6 months
- •Existing pregnancy or lactation
- •childbearing or fertility without using recognized safe methods of contraception
- •Coexisting other malignant diseases with the exception of a non-melanomatuous, localized skin tumor or carcinoma in situ of the cervix
- •absence of a signed consent form
研究组 & 干预措施
Non-Responder
Oxaliplatin Epirubicin Capecitabine 5-FU Carboplatin Paclitaxel Radiation Biopsy
干预措施: Oxaliplatin (Drug)
Non-Responder
Oxaliplatin Epirubicin Capecitabine 5-FU Carboplatin Paclitaxel Radiation Biopsy
干预措施: Biopsy (Procedure)
Non-Responder
Oxaliplatin Epirubicin Capecitabine 5-FU Carboplatin Paclitaxel Radiation Biopsy
干预措施: Epirubicin (Drug)
Non-Responder
Oxaliplatin Epirubicin Capecitabine 5-FU Carboplatin Paclitaxel Radiation Biopsy
干预措施: Capecitabine (Drug)
Non-Responder
Oxaliplatin Epirubicin Capecitabine 5-FU Carboplatin Paclitaxel Radiation Biopsy
干预措施: 5-FU (Drug)
Non-Responder
Oxaliplatin Epirubicin Capecitabine 5-FU Carboplatin Paclitaxel Radiation Biopsy
干预措施: Carboplatin (Drug)
Non-Responder
Oxaliplatin Epirubicin Capecitabine 5-FU Carboplatin Paclitaxel Radiation Biopsy
干预措施: Paclitaxel (Drug)
Non-Responder
Oxaliplatin Epirubicin Capecitabine 5-FU Carboplatin Paclitaxel Radiation Biopsy
干预措施: radiation (Radiation)
Responder
Oxaliplatin Epirubicin Capecitabine 5-FU Biopsy
干预措施: Oxaliplatin (Drug)
Responder
Oxaliplatin Epirubicin Capecitabine 5-FU Biopsy
干预措施: Epirubicin (Drug)
Responder
Oxaliplatin Epirubicin Capecitabine 5-FU Biopsy
干预措施: Capecitabine (Drug)
Responder
Oxaliplatin Epirubicin Capecitabine 5-FU Biopsy
干预措施: 5-FU (Drug)
Responder
Oxaliplatin Epirubicin Capecitabine 5-FU Biopsy
干预措施: Biopsy (Procedure)
结局指标
主要结局
R0 resection rate
时间窗: 1 day of surgery (in between day 28 to day 43 after radio-chemotherapy)
R0 resection rate of patients suffering from metabolically (following PET criteria) chemotherapy-resistant, locally advanced AEG, who receive a more intensive neoadjuvant radio-chemotherapy (INRCT)
次要结局
- Regression(1 day of surgery (in between day 28 to day 43 after radio-chemotherapy))
- Overall survival(from day 0 to follow up visit 6 (24 months after surgery))
- Metabilic response rate(from day 0 to one time point of time period day 14 to 28 after chemotherapy)
- Disease-free survival(from day 0 to follow up visit 6 (24 months after surgery))
- QLQ-C30(from day 0 to follow up visit 6 (24 months after surgery))
- Translational analysis(1 day of surgery (in between day 28 to day 43 after radio-chemotherapy))
- QLQ-OG25(from day 0 to follow up visit 6 (24 months after surgery))
- Adverse Events(from day 0 to follow up visit 6 (24 months after surgery))