folfox6 versus mfolfirinox as first line chemotherapy in metastatic gastric cancer or esophagogastric junction adenocarcinoma (type ii-iii)

Conditions: Gastric Carcinoma Stage IV; Esophagogastric Junction Adenocarcinoma Stage IV

Summary: patients with metastatic adenocarcinoma of the stomach or the esophagogastric junction (ii-iii type by siewert) without previous therapy will be treated with one of two chemotherapy combinations . one half of the patients gets 5-fluorouracil (5-fu), leucovorin, oxaliplatin (folfox6), the others 5-fluorouracil (5-fu), leucovorin, oxaliplatin and irinotecan (mfolfirinox). main objective of the study is progression free survival.

this parallel, randomized, open-label study 326 patients with metastatic ( adenocarcinoma of the stomach or the esophagogastric junction without previous therapy will be included in this study. after randomization patients receive 9 cycles folfox6 or mfolfirinox. stratification factors include ecog, site of metastasis, age, pathological subtypes. efficacy will be evaluated every 3 cycles with recist. toxicity will be assessed with who ctc 3.0 every 2 weeks.

Eligibility criteria:
inclusion criteria: 1. histologically confirmed locally advanced, recurrent or metastatic adenocarcinoma of the esophagogastric junction (siewert type ii-iii) or the stomach 2. no prior palliative chemotherapy or radiation therapy 3. age 18-70 years (female and male) 4. eastern cooperative oncology group ≤ 2 5. neutrophils\> 2.000/µl 6. platelets \> 100.000/µl 7. normal value of serum creatinin 8. albumin level \> 29 г/л 9. aspartate transaminase (ast) or alanine transaminase (alt) less than 3 times the upper limits of normal (uln) 10. total bilirubin less than 1.5 times the uln 11. written informed consent. exclusion criteria: 1. previous palliative cytostatic chemotherapy 2. cancer relapse 3. complicated gastric cancer (perforation, bleeding, sub or decompensated stenosis, dysphagia iv) 4. diarrhea ≥ 2 according to the criteria of common terminology criteria for adverse events (ctcae) version 4.1; 5. hypersensitivity against 5- fluorouracil, leucovorin, oxaliplatin, irinotecan 6. existence of contraindications against 5- fluorouracil, leucovorin, oxaliplatin, irinotecan or docetaxel 7. active coronary heart disease, cardiomyopathy or cardiac insufficiency stage iii-iv according to new york heart association (nyha) 8. severe non-surgical accompanying disease or acute infection (uncontrolled arterial hypertension, diabetes mellitus, stroke less than 6 months old, mental disorders, other tumors and others) 9. malignant secondary disease, dated back \< 5 years (exception: in-situ-carcinoma of the cervix uteri, adequately treated skin basal cell carcinoma) 10. peripheral polyneuropathy \> grad ii 11. liver dysfunction (ast)/alt\>3,0xuln, alt\>3xuln, bilirubin\>1,5xuln) serum creatinin \>1,0xuln 12. chronic inflammable gastro-intestinal disease 13. inclusion in another clinical trial 14. pregnancy or lactation 15. hepatitis b or c in the active stage 16. human immunodeficiency virus(hiv) infected 17. serious concomitant somatic and mental illnesses / deviations or territorial causes that may prevent the patient from participating in the protocol and observing the protocol schedule 18. foreigners or persons with limited legal status