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

Primary Purpose

Adenocarcinoma of the Esophagogastric Junction

Status
Unknown status
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Oxaliplatin
Epirubicin
Capecitabine
5-FU
Carboplatin
Paclitaxel
radiation
Biopsy
Sponsored by
Technical University of Munich
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adenocarcinoma of the Esophagogastric Junction focused on measuring Potentially R0 - resectable AEG and primary tumor category, Histologically confirmed AEG I-III, Functional operability, Intense FDG tracer uptake of the tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Non-Responder

Responder

Arm Description

Oxaliplatin Epirubicin Capecitabine 5-FU Carboplatin Paclitaxel Radiation Biopsy

Oxaliplatin Epirubicin Capecitabine 5-FU Biopsy

Outcomes

Primary Outcome Measures

R0 resection rate
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

Regression
Histological regression defined by Becker Criteria
Overall survival
Overall survival defined as period from start of study to death (if necessary censored by end of follow-up period)
Disease-free survival
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"
Quality of life
Quality of life, analyzed via EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires
Metabilic response rate
Metabolic response rate under neoadjuvant chemotherapy
Translational analysis
Translational analysis for identification of tumor determinants relevant for prognosis and therapy
Adverse Events
Occurence of AEs

Full Information

First Posted
October 7, 2014
Last Updated
September 21, 2018
Sponsor
Technical University of Munich
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1. Study Identification

Unique Protocol Identification Number
NCT02287129
Brief Title
Evaluation for the Individualization of Therapy in Adenocarcinomas of the Gastroesophageal Junction
Acronym
MEMORI
Official Title
Metabolic and Molecular Response Evaluation for the Individualization of Therapy in Adenocarcinomas of the Gastroesophageal Junction
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Unknown status
Study Start Date
November 2014 (undefined)
Primary Completion Date
December 2018 (Anticipated)
Study Completion Date
June 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Technical University of Munich

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenocarcinoma of the Esophagogastric Junction
Keywords
Potentially R0 - resectable AEG and primary tumor category, Histologically confirmed AEG I-III, Functional operability, Intense FDG tracer uptake of the tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Non-Responder
Arm Type
Experimental
Arm Description
Oxaliplatin Epirubicin Capecitabine 5-FU Carboplatin Paclitaxel Radiation Biopsy
Arm Title
Responder
Arm Type
Active Comparator
Arm Description
Oxaliplatin Epirubicin Capecitabine 5-FU Biopsy
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
Oxaliplan
Intervention Description
130 mg/m2
Intervention Type
Drug
Intervention Name(s)
Epirubicin
Other Intervention Name(s)
Epi Teva
Intervention Description
50 mg/m2
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
625 mg/m2
Intervention Type
Drug
Intervention Name(s)
5-FU
Other Intervention Name(s)
5-FU medac
Intervention Description
200 mg/m2
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Carboplatin SUN
Intervention Description
2 mg/ml min
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Taxomedac
Intervention Description
50 mg/m2
Intervention Type
Radiation
Intervention Name(s)
radiation
Other Intervention Name(s)
intensitive neoadjuvant radiochemotherapy (INRCT)
Intervention Description
total dosage 41,4 Gy
Intervention Type
Procedure
Intervention Name(s)
Biopsy
Other Intervention Name(s)
esophagogastroduodenoscopy
Intervention Description
translational analysis
Primary Outcome Measure Information:
Title
R0 resection rate
Description
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)
Time Frame
1 day of surgery (in between day 28 to day 43 after radio-chemotherapy)
Secondary Outcome Measure Information:
Title
Regression
Description
Histological regression defined by Becker Criteria
Time Frame
1 day of surgery (in between day 28 to day 43 after radio-chemotherapy)
Title
Overall survival
Description
Overall survival defined as period from start of study to death (if necessary censored by end of follow-up period)
Time Frame
from day 0 to follow up visit 6 (24 months after surgery)
Title
Disease-free survival
Description
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"
Time Frame
from day 0 to follow up visit 6 (24 months after surgery)
Title
Quality of life
Description
Quality of life, analyzed via EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires
Time Frame
from day 0 to follow up visit 6 (24 months after surgery)
Title
Metabilic response rate
Description
Metabolic response rate under neoadjuvant chemotherapy
Time Frame
from day 0 to one time point of time period day 14 to 28 after chemotherapy
Title
Translational analysis
Description
Translational analysis for identification of tumor determinants relevant for prognosis and therapy
Time Frame
1 day of surgery (in between day 28 to day 43 after radio-chemotherapy)
Title
Adverse Events
Description
Occurence of AEs
Time Frame
from day 0 to follow up visit 6 (24 months after surgery)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jens Siveke, Prof. Dr.
Organizational Affiliation
II. Medizinische Klinik, Klinikum rechts der Isar (MRI) der TUM,Ismaninger Str. 22
Official's Role
Principal Investigator
Facility Information:
Facility Name
2nd department of the Medical Clinic of the Technical University Munich
City
Munich
State/Province
Bavaria
ZIP/Postal Code
81675
Country
Germany

12. IPD Sharing Statement

Learn more about this trial

Evaluation for the Individualization of Therapy in Adenocarcinomas of the Gastroesophageal Junction

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