FOLFOX6 Versus mFOLFIRINOX as First Line Chemotherapy in Metastatic Gastric Cancer or Esophagogastric Junction Adenocarcinoma (Type II-III)

Blokhin's Russian Cancer Research Center326 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

326

Conditions

Gastric Carcinoma Stage IV Esophagogastric Junction Adenocarcinoma Stage IV

IrinotecanDRUG

d1 Irinotecan 180mg/m² every two weeks

OxaliplatinDRUG

d1 Oxaliplatin 85 mg/m² every two weeks

5-FUDRUG

d1-2 5-FU 2200 mg/m² every two weeks

5-FUDRUG

d1 5-FU 250 mg/m² every two weeks

LeucovorinDRUG

d1 Leucovorin 400 mg every two weeks

5-FUDRUG

d1 5-FU 400 mg/m² every two weeks

5-FUDRUG

d1-2 5-FU 2400 mg/m² every two weeks

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Progression-Free Survival

PFS is defined as the time from the date of randomization to the date of the first documentation of progressive disease or date of death, whichever occurs first. For target lesions (TL), PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD) of TLs, taking as a reference the smallest SLD recorded since the treatment started, or the appearance of one or more lesions. For non-target lesions (NTL), PD was defined as an unequivocal progression of existing NTLs. Participants were censored at the last date of tumor measurement, the last date in the study drug log, or the date of last follow-up.

Time frame: 36 months

Secondary Outcomes

Overall Survival (OS)

OS is defined as the time from the date of randomization to the date of death due to any cause. Participants were censored at the last date of tumor measurement, the last date in the study drug log or the date of last follow-up

Time frame: 60 months

Percentage of Participants With Confirmed Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST)

Time frame: 12 months

Duration of Response

Time frame: 12 months

Treatment associated toxicities

WHO CTC 3.0

Time frame: 12 months

FOLFOX6 Versus mFOLFIRINOX as First Line Chemotherapy in Metastatic Gastric Cancer or Esophagogastric Junction Adenocarcinoma (Type II-III)

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts