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

Phase 2
Recruiting
Conditions
Gastric Carcinoma Stage IV
Esophagogastric Junction Adenocarcinoma Stage IV
Interventions
Registration Number
NCT04442984
Lead Sponsor
Blokhin's Russian Cancer Research Center
Brief 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.

Detailed Description

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
326
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
mFOLFIRINOXIrinotecanIrinotecan 180mg/m2 d1, 5FU 250mg/m2 iv bolus d1, 5-FU 2200 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles
mFOLFIRINOX5-FUIrinotecan 180mg/m2 d1, 5FU 250mg/m2 iv bolus d1, 5-FU 2200 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles
FOLFOX6Leucovorin5FU 400mg/m2 iv bolus d1, 5-FU 2400 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles
FOLFOX6Oxaliplatin5FU 400mg/m2 iv bolus d1, 5-FU 2400 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles
FOLFOX65-FU5FU 400mg/m2 iv bolus d1, 5-FU 2400 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles
mFOLFIRINOXOxaliplatinIrinotecan 180mg/m2 d1, 5FU 250mg/m2 iv bolus d1, 5-FU 2200 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles
mFOLFIRINOXLeucovorinIrinotecan 180mg/m2 d1, 5FU 250mg/m2 iv bolus d1, 5-FU 2200 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles
Primary Outcome Measures
NameTimeMethod
Progression-Free Survival36 months

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.

Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS)60 months

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

Percentage of Participants With Confirmed Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST)12 months
Duration of Response12 months
Treatment associated toxicities12 months

WHO CTC 3.0

Trial Locations

Locations (1)

Blokhin's Russian Cancer Research Center

🇷🇺

Moscow, Russian Federation

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