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

Sponsor

Blokhin's Russian Cancer Research Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04442984

Collaborator

(none)

326

Enrollment

Location

Arms

Anticipated Duration (Months)

5.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gastric Carcinoma Stage IV Esophagogastric Junction Adenocarcinoma Stage IV	Drug: Irinotecan Drug: Oxaliplatin Drug: 5-FU Drug: 5-FU Drug: Leucovorin Drug: 5-FU Drug: 5-FU	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

326 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

FOLFOX6 Versus mFOLFIRINOX as First Line Chemotherapy in Metastatic Gastric or Esophagogastric Junction Adenocarcinoma (Type II-III): Open-label Randomized Phase 2/3 Trial

Actual Study Start Date :

Nov 3, 2019

Anticipated Primary Completion Date :

Nov 3, 2021

Anticipated Study Completion Date :

Nov 3, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: FOLFOX6 5FU 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	Drug: Oxaliplatin d1 Oxaliplatin 85 mg/m² every two weeks Drug: Leucovorin d1 Leucovorin 400 mg every two weeks Drug: 5-FU d1 5-FU 400 mg/m² every two weeks Drug: 5-FU d1-2 5-FU 2400 mg/m² every two weeks
Experimental: mFOLFIRINOX Irinotecan 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	Drug: Irinotecan d1 Irinotecan 180mg/m² every two weeks Drug: Oxaliplatin d1 Oxaliplatin 85 mg/m² every two weeks Drug: 5-FU d1-2 5-FU 2200 mg/m² every two weeks Drug: 5-FU d1 5-FU 250 mg/m² every two weeks Drug: Leucovorin d1 Leucovorin 400 mg every two weeks

Arm

Intervention/Treatment

Active Comparator: FOLFOX6

5FU 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

Drug: Oxaliplatin

d1 Oxaliplatin 85 mg/m² every two weeks

Drug: Leucovorin

d1 Leucovorin 400 mg every two weeks

Drug: 5-FU

d1 5-FU 400 mg/m² every two weeks

Drug: 5-FU

d1-2 5-FU 2400 mg/m² every two weeks

Experimental: mFOLFIRINOX

Irinotecan 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

Drug: Irinotecan

d1 Irinotecan 180mg/m² every two weeks

Drug: Oxaliplatin

d1 Oxaliplatin 85 mg/m² every two weeks

Drug: 5-FU

d1-2 5-FU 2200 mg/m² every two weeks

Drug: 5-FU

d1 5-FU 250 mg/m² every two weeks

Drug: Leucovorin

d1 Leucovorin 400 mg every two weeks

Outcome Measures

Primary Outcome Measures

Progression-Free Survival [36 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

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 Response [12 months]
Treatment associated toxicities [12 months]
WHO CTC 3.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

histologically confirmed locally advanced, recurrent or metastatic adenocarcinoma of the esophagogastric junction (Siewert type II-III) or the stomach
no prior palliative chemotherapy or radiation therapy
Age 18-70 years (female and male)
Eastern Cooperative Oncology Group ≤ 2
Neutrophils> 2.000/µl
Platelets > 100.000/µl
Normal value of Serum Creatinin
Albumin level > 29 г/л
Aspartate transaminase (AST) or alanine transaminase (ALT) less than 3 times the upper limits of normal (ULN)
Total Bilirubin less than 1.5 times the ULN
Written informed consent.

Exclusion Criteria:

Previous palliative cytostatic chemotherapy
Cancer relapse
Complicated gastric cancer (perforation, bleeding, sub or decompensated stenosis, dysphagia IV)
Diarrhea ≥ 2 according to the criteria of Common Terminology Criteria for Adverse Events (CTCAE) version 4.1;
Hypersensitivity against 5- Fluorouracil, Leucovorin, Oxaliplatin, irinotecan
Existence of contraindications against 5- Fluorouracil, Leucovorin, Oxaliplatin, Irinotecan or Docetaxel
Active coronary heart disease, Cardiomyopathy or cardiac insufficiency stage III-IV according to New York Heart Association (NYHA)
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)
Malignant secondary disease, dated back < 5 years (exception: In-situ-carcinoma of the cervix uteri, adequately treated skin basal cell carcinoma)
Peripheral polyneuropathy > Grad II
Liver dysfunction (AST)/ALT>3,0xULN, ALT>3xULN, Bilirubin>1,5xULN) Serum Creatinin

1,0xULN

Chronic inflammable gastro-intestinal disease
Inclusion in another clinical trial
Pregnancy or lactation
Hepatitis B or C in the active stage
Human immunodeficiency virus(HIV) infected
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
Foreigners or persons with limited legal status