Evaluation for the Individualization of Therapy in Adenocarcinomas of the Gastroesophageal Junction (MEMORI)

Technical University of Munich

Status and phase: Completed; Phase 2

Conditions: Adenocarcinoma of the Esophagogastric Junction

Treatments: Drug: Epirubicin; Drug: 5-FU; Drug: Carboplatin; Drug: Paclitaxel; Procedure: Biopsy; Drug: Capecitabine; Radiation: radiation; Drug: Oxaliplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT02287129

MEM-0000-SIV-0028-I

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 75 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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75 participants in 2 patient groups

Non-Responder

Experimental group

Description:

Oxaliplatin Epirubicin Capecitabine 5-FU Carboplatin Paclitaxel Radiation Biopsy

Treatment:

Drug: Oxaliplatin

Radiation: radiation

Drug: Capecitabine

Procedure: Biopsy

Drug: Paclitaxel

Drug: Carboplatin

Drug: 5-FU

Drug: Epirubicin

Responder

Active Comparator group

Description:

Oxaliplatin Epirubicin Capecitabine 5-FU Biopsy

Treatment:

Drug: Oxaliplatin

Drug: Capecitabine

Procedure: Biopsy

Drug: 5-FU

Drug: Epirubicin