Clinical trial NCT02287129: Evaluation for the Individualization of Therapy in Adenocarcinomas of the Gastroesophageal Junction
Official title: Metabolic and Molecular Response Evaluation for the Individualization of Therapy in Adenocarcinomas of the Gastroesophageal Junction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Technical University of Munich
Sponsor class: OTHER
First posted: 2014-11-10
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: R0 resection rate
timeFrame: 1 day of surgery (in between day 28 to day 43 after radio-chemotherapy)
Secondary outcomes:
measure: Regression
timeFrame: 1 day of surgery (in between day 28 to day 43 after radio-chemotherapy)
measure: Overall survival
timeFrame: from day 0 to follow up visit 6 (24 months after surgery)
measure: Disease-free survival
timeFrame: from day 0 to follow up visit 6 (24 months after surgery)
measure: QLQ-C30
timeFrame: from day 0 to follow up visit 6 (24 months after surgery)
measure: Metabilic response rate
timeFrame: from day 0 to one time point of time period day 14 to 28 after chemotherapy
measure: Translational analysis
timeFrame: 1 day of surgery (in between day 28 to day 43 after radio-chemotherapy)
measure: Adverse Events
timeFrame: from day 0 to follow up visit 6 (24 months after surgery)
measure: QLQ-OG25
timeFrame: from day 0 to follow up visit 6 (24 months after surgery)
Other outcomes:
Locations:
city: Munich
country: Germany
facility: 2nd department of the Medical Clinic of the Technical University Munich
state: Bavaria
Study officials:
affiliation: II. Medizinische Klinik, Klinikum rechts der Isar (MRI) der TUM,Ismaninger Str. 22
name: Jens Siveke, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: