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

Adenocarcinoma of the Esophagogastric Junction Clinical Trial

— MEMORI  

Official title:

Metabolic and Molecular Response Evaluation for the Individualization of Therapy in Adenocarcinomas of the Gastroesophageal Junction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02287129
• Other study ID #: MEM-0000-SIV-0028-I
• Status: Completed
• Phase: Phase 2
• Start date: December 5, 2014
• Est. completion date: August 7, 2020

Study information

• Verified date: November 2023
• Source: Technical University of Munich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: August 7, 2020
• Est. primary completion date: August 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Esophagogastric Junction

Intervention

Drug:
• Oxaliplatin
130 mg/m2
• Epirubicin
50 mg/m2
• Capecitabine
625 mg/m2
• 5-FU
200 mg/m2
• Carboplatin
2 mg/ml min
• Paclitaxel
50 mg/m2

Radiation:
• radiation
total dosage 41,4 Gy

Procedure:
• Biopsy
translational analysis

Locations

Country	Name	City	State
Germany	2nd department of the Medical Clinic of the Technical University Munich	Munich	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
Technical University of Munich

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	1 day of surgery (in between day 28 to day 43 after radio-chemotherapy)
Secondary	Regression	Histological regression defined by Becker Criteria	1 day of surgery (in between day 28 to day 43 after radio-chemotherapy)
Secondary	Overall survival	Overall survival defined as period from start of study to death (if necessary censored by end of follow-up period)	from day 0 to follow up visit 6 (24 months after surgery)
Secondary	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"	from day 0 to follow up visit 6 (24 months after surgery)
Secondary	QLQ-C30	Quality of life, analyzed via EORTC QLQ-C30 questionnaires	from day 0 to follow up visit 6 (24 months after surgery)
Secondary	Metabilic response rate	Metabolic response rate under neoadjuvant chemotherapy	from day 0 to one time point of time period day 14 to 28 after chemotherapy
Secondary	Translational analysis	Translational analysis for identification of tumor determinants relevant for prognosis and therapy	1 day of surgery (in between day 28 to day 43 after radio-chemotherapy)
Secondary	Adverse Events	Occurence of AEs	from day 0 to follow up visit 6 (24 months after surgery)
Secondary	QLQ-OG25	Quality of life, analyzed via EORTC QLQ-OG25 questionnaires	from day 0 to follow up visit 6 (24 months after surgery)