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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02287129
Recruitment Status : Active, not recruiting
First Posted : November 10, 2014
Last Update Posted : September 25, 2018
Sponsor:
Information provided by (Responsible Party):
Technische Universität München

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.

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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

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




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



Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02287129


Locations
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Germany
2nd department of the Medical Clinic of the Technical University Munich
Munich, Bavaria, Germany, 81675
Sponsors and Collaborators
Technische Universität München
Investigators
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Principal Investigator: Jens Siveke, Prof. Dr. II. Medizinische Klinik, Klinikum rechts der Isar (MRI) der TUM,Ismaninger Str. 22

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Responsible Party: Technische Universität München
ClinicalTrials.gov Identifier: NCT02287129    
Other Study ID Numbers: MEM-0000-SIV-0028-I
First Posted: November 10, 2014    Key Record Dates
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:
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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