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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastric Carcinoma Stage IV; Esophagogastric Junction Adenocarcinoma Stage IV
• Intervention / Treatment: Drug: Irinotecan; Drug: Oxaliplatin; Drug: 5-FU; Drug: 5-FU; Drug: Leucovorin; Drug: 5-FU; Drug: 5-FU

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 Type: Interventional
• Enrollment (Anticipated): 326
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tatiana Titova; Phone Number: +79152982811; Email: tatiana.titovadoc@gmail.com

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115478
    • Recruiting
    • Blokhin's Russian Cancer Research Center
    • Contact: Tatiana Titova; Phone Number: +79152982811; Email: tatiana.titovadoc@gmail.com
    • Principal Investigator: Artamonova Elena

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: 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; 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; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response		12 months
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	60 months
Percentage of Participants With Confirmed Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST)		12 months
Treatment associated toxicities	WHO CTC 3.0	12 months

Collaborators and Investigators

• Sponsor: Blokhin's Russian Cancer Research Center

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2019
• Primary Completion (Anticipated): November 3, 2021
• Study Completion (Anticipated): November 3, 2024

Study Registration Dates

• First Submitted: June 17, 2020
• First Submitted That Met QC Criteria: June 19, 2020
• First Posted (Actual): June 23, 2020

Study Record Updates

• Last Update Posted (Actual): April 13, 2021
• Last Update Submitted That Met QC Criteria: April 11, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan
• Other Study ID Numbers: 2020-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No