Prospective Study With FLOT in Patients With Locally Advanced, Limited Metastatic or Extensive Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction

Study Overview
=================
Brief Summary
-----------------
Patients with locally advanced or metastatic gastric carcinoma or carcinoma of the esophagogastric junction without prior palliative therapy will be treated with 8 cycles of the FLOT scheme (up to 12 cycles if the response is favourable). Prior to enrollment a unique and detailed clinical evaluation of the dissemination of the disease will be done which includes a differentiated regard of the metastatic status. patients will be classified as having either (A) locally advanced, (B) limited metastatic, or (C) extensive metastatic disease. In arms A and B surgical intervention is planned if operability is reached. The hypothesis is that by classifying patients more individually by the state of their disease, patients in arm B will have a significantly prolonged overall survival compared to patients in arm C.

Detailed Description
-----------------
250 patients with locally advanced or metastatic gastric carcinoma or carcinoma of the esophagogastric junction without prior palliative therapy will be treated with 8 cycles of the FLOT scheme (up to 12 cycles if the response is favourable). Prior to enrolment a unique and detailed clinical evaluation of the dissemination of the disease will be done which includes a differentiated regard of the M-category in the TNM classification. A prospective stratification will classify the patients as having either (A) locally advanced, (B) limited metastatic, or (C) extensive metastatic disease. In addition, the pharmacogenetic risk profile of the patients will be evaluated by a combined analysis of two genetic polymorphisms of the metabolism of the applied substances (XPD312, GSTT1). For the assessment of the disease, reference regions are examined by CT or MRI scans and if applicable endoscopy prior to the start of the study, every 2 months during and after the end of therapy until progression of the disease occurs. Evaluation of quality of life (by standard forms like EORTC-Q30 and others) is continued after progression. Clinical examinations (blood count, assessment of toxicity, anamnesis) is performed every two weeks for evaluation of toxicity and application of chemotherapy. After informed consent is given, peripheral blood of the patient will be analysed for the pharmacogenetic risk profile. Representative tumor material will be analysed by immunohistochemistry and quantitative PCR for the expression of several molecular factors.

Official Title
-----------------
A Prospective Multicenter Study With 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) in Patients With Locally Advanced, Limited Metastatic or Extensive Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction

Conditions
-----------------
Gastric Cancer, Adenocarcinoma of the Esophagogastric Junction

Intervention / Treatment
-----------------
* Drug: Docetaxel
* Drug: 5-Fluorouracil
* Drug: Oxaliplatin
* Drug: folinic acid


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Metastatic or locally advanced gastric cancer or adenocarcinoma of the esophagogastric junction No prior chemotherapy in metastatic state Adequate blood and biochemistry parameters Exclusion Criteria: Hypersensitivity for 5-FU, Leucovorin, Oxaliplatin or Docetaxel KHK, cardiomyopathy or cardiac insufficiency Malignancy <5 years ago Brain metastases Severe internal disease or inadequate blood and biochemistry parameters Pregnancy and lactation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FLOT<br> | Drug: Docetaxel<br>* 50mg/m2 qd15<br>Drug: 5-Fluorouracil<br>* 2600mg/m2 qd15<br>Drug: Oxaliplatin<br>* 85mg/m2 qd15<br>Drug: folinic acid<br>* 200mg/m2 qd15<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | every 2 weeks during study, every 3 months follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacogenetic risk profile |  | once at beginning | 
| Quality of Life |  | every 8 weeks | 
| Progression free survival (PFS) and response rate (Stratum B and C) |  | every 8 weeks | 
| rate of R0-resections, rate of pathological remissions and perioperative morbidity and mortality in stratum A and B Perioperative Morbidität und Mortalität in dem Arm A und ggf. B |  | after surgical intervention |