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

• ClinicalTrials.gov Identifier: NCT02287129
• Recruitment Status: Active, not recruiting
• First Posted: November 10, 2014
• Last Update Posted: September 25, 2018
• Sponsor: Technische Universität München
• Information provided by (Responsible Party): Technische Universität München

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Adenocarcinoma of the Esophagogastric Junction	Drug: Oxaliplatin; Drug: Epirubicin; Drug: Capecitabine; Drug: 5-FU; Drug: Carboplatin; Drug: Paclitaxel; Radiation: radiation; Procedure: Biopsy	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 75 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Metabolic and Molecular Response Evaluation for the Individualization of Therapy in Adenocarcinomas of the Gastroesophageal Junction
• Study Start Date: November 2014
• Estimated Primary Completion Date: December 2018
• Estimated Study Completion Date: June 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Non-Responder; Oxaliplatin Epirubicin Capecitabine 5-FU Carboplatin Paclitaxel Radiation Biopsy	Drug: Oxaliplatin; 130 mg/m2; Other Name: Oxaliplan; Drug: Epirubicin; 50 mg/m2; Other Name: Epi Teva; Drug: Capecitabine; 625 mg/m2; Other Name: Xeloda; Drug: 5-FU; 200 mg/m2; Other Name: 5-FU medac; Drug: Carboplatin; 2 mg/ml min; Other Name: Carboplatin SUN; Drug: Paclitaxel; 50 mg/m2; Other Name: Taxomedac; Radiation: radiation; total dosage 41,4 Gy; Other Name: intensitive neoadjuvant radiochemotherapy (INRCT); Procedure: Biopsy; translational analysis; Other Name: esophagogastroduodenoscopy
Active Comparator: Responder; Oxaliplatin Epirubicin Capecitabine 5-FU Biopsy	Drug: Oxaliplatin; 130 mg/m2; Other Name: Oxaliplan; Drug: Epirubicin; 50 mg/m2; Other Name: Epi Teva; Drug: Capecitabine; 625 mg/m2; Other Name: Xeloda; Drug: 5-FU; 200 mg/m2; Other Name: 5-FU medac; Procedure: Biopsy; translational analysis; Other Name: esophagogastroduodenoscopy

Outcome Measures

Primary Outcome Measures :

1. R0 resection rate [ Time Frame: 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)

Secondary Outcome Measures :

1. Regression [ Time Frame: 1 day of surgery (in between day 28 to day 43 after radio-chemotherapy) ]
   Histological regression defined by Becker Criteria
2. Overall survival [ Time Frame: from day 0 to follow up visit 6 (24 months after surgery) ]
   Overall survival defined as period from start of study to death (if necessary censored by end of follow-up period)
3. Disease-free survival [ Time Frame: from day 0 to follow up visit 6 (24 months after surgery) ]
   Disease-free survival, defined as period from start of study to earlier occurring event: death or relapse until end of follow-up; Relapse will be separated into events of "local failure", "distant failure" and "local and distant failure"
4. Quality of life [ Time Frame: from day 0 to follow up visit 6 (24 months after surgery) ]
   Quality of life, analyzed via EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires
5. Metabilic response rate [ Time Frame: from day 0 to one time point of time period day 14 to 28 after chemotherapy ]
   Metabolic response rate under neoadjuvant chemotherapy
6. Translational analysis [ Time Frame: 1 day of surgery (in between day 28 to day 43 after radio-chemotherapy) ]
   Translational analysis for identification of tumor determinants relevant for prognosis and therapy
7. Adverse Events [ Time Frame: from day 0 to follow up visit 6 (24 months after surgery) ]
   Occurence of AEs

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Germany

2nd department of the Medical Clinic of the Technical University Munich

Munich, Bavaria, Germany, 81675

Sponsors and Collaborators

Technische Universität München

Investigators

• Principal Investigator: Jens Siveke, Prof. Dr.; II. Medizinische Klinik, Klinikum rechts der Isar (MRI) der TUM,Ismaninger Str. 22

More Information

• Responsible Party: Technische Universität München
• ClinicalTrials.gov Identifier: NCT02287129
• Other Study ID Numbers: MEM-0000-SIV-0028-I
• First Posted: November 10, 2014
• Last Update Posted: September 25, 2018
• Last Verified: September 2018

Keywords provided by Technische Universität München:

Potentially R0 - resectable AEG and primary tumor category; Histologically confirmed AEG I-III; Functional operability; Intense FDG tracer uptake of the tumor

Additional relevant MeSH terms:

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Paclitaxel; Carboplatin; Capecitabine; Oxaliplatin; Epirubicin; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors