FOLFIRINOX vs FLOT Chemotherapy for Resectable Gastric or Esophagogastric Junction Adenocarcinoma (RusGCG-01)

Perioperative Chemotherapy With FOLFIRINOX Regimen or FLOT Regimen for Resectable Gastric or Esophagogastric Junction Adenocarcinoma (Type II-III): Open-label Randomized Phase 2/3 Trial

Patients with resectable 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 before and after surgery. One half of the patients gets 5-Fluorouracil (5-FU), Leucovorin, Oxaliplatin and Docetaxel (FLOT), the others 5-Fluorouracil (5-FU), Leucovorin, Oxaliplatin and Irinotecan (FOLFIRINOX). Main objective of the study is median overall survival.

Study Overview

• Status: Recruiting
• Conditions: Stomach Neoplasms; Gastrointestinal Neoplasms; Docetaxel; Oxaliplatin; Fluoruracil; Irinotecan Hydrochloride
• Intervention / Treatment: Drug: Irinotecan; Drug: 5-FU; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Docetaxel

Detailed Description

538 Patients with resectable (cT4cN0 or cT1-4 and cN+, cM0) adenocarcinoma of the stomach or the esophagogastric junction without previous therapy will be included in this study. After randomization patients receive perioperatively 4 cycles FLOT or FOLFIRINOX, followed by a restaging of the tumour status and surgery. Subsequently another 4 cycles of FLOT or FOLFIRNOX are applicated.

• Study Type: Interventional
• Enrollment (Anticipated): 538
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Aleksei Kalinin, Phd; Phone Number: +79197681276; Email: kalininalexey1986@yandex.ru
• Study Contact Backup: Name: Sergey Nered, Phd; Phone Number: +79031995078; Email: nered@mail.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115478
    • Recruiting
    • Aleksei Kalinin
    • Contact: Aleksei Kalinin; Phone Number: +79197681276; Email: kalininalexey1986@yandex.ru
    • Principal Investigator: Ivan Stilidi, Phd
    • Principal Investigator: Sergey Nered, Phd
    • Principal Investigator: Aleksei Kalinin, Phd
    • Principal Investigator: Natalya Besova, Phd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. сT4 cN0 or cT1-4 cN+ histologically proven adenocarcinoma of the esophagogastric junction (Siewert type II-III) or the stomach without distant metastases (M0)
2. No previous cytostatic chemotherapy or radiation therapy
3. Age 18-70 years (female and male)
4. Eastern Cooperative Oncology Group ≤ 2
5. Surgical resectability
6. Neutrophils> 2.000/µl
7. Platelets > 100.000/µl
8. Normal value of Serum Creatinin
9. Albumin level > 29 г/л
10. Aspartate transaminase (AST) or alanine transaminase (ALT) less than 3 times the upper limits of normal (ULN)
11. Total Bilirubin less than 1.5 times the ULN
12. Written informed consent.

Exclusion Criteria:

1. Previous cytostatic chemotherapy or radiation therapy
2. Distant metastases or all primarily not resectable stages
3. Cancer relapse
4. Complicated gastric cancer (perforation, bleeding, sub or decompensated stenosis, dysphagia IV)
5. Diarrhea ≥ 2 according to the criteria of Common Terminology Criteria for Adverse Events (CTCAE) version 4.1;
6. Hypersensitivity against 5- Fluorouracil, Leucovorin, Oxaliplatin, Epirubicin and Docetaxel
7. Existence of contraindications against 5- Fluorouracil, Leucovorin, Oxaliplatin, Irinotecan or Docetaxel
8. Active coronary heart disease, Cardiomyopathy or cardiac insufficiency stage III-IV according to New York Heart Association (NYHA)
9. 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)
10. Malignant secondary disease, dated back < 5 years (exception: In-situ-carcinoma of the cervix uteri, adequately treated skin basal cell carcinoma)
11. Peripheral polyneuropathy > Grad II
12. Liver dysfunction (AST)/ALT>3,0xULN, ALT>3xULN, Bilirubin>1,5xULN)
13. Serum Creatinin >1,0xULN
14. Chronic inflammable gastro-intestinal disease
15. Inclusion in another clinical trial
16. Pregnancy or lactation
17. Hepatitis B or C in the active stage
18. Human immunodeficiency virus(HIV) infected
19. 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
20. 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
Experimental: FOLFIRINOX; Irinotecan 180mg/m2 d1, d1-2 5-FU 2450 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m², d1 every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP	Drug: Irinotecan; d1 Irinotecan 180mg/m² every two weeks; Drug: 5-FU; d1-2 5-FU 2450 mg/m² every two weeks; Drug: Leucovorin; d1 Leucovorin 200 mg/m² every two weeks; Drug: Oxaliplatin; d1 Oxaliplatin 85 mg/m² every two weeks
Active Comparator: FLOT; d1 Docetaxel 50mg/m2, d1-2 5-FU 2600 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m² every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP	Drug: 5-FU; d1-2 5-FU 2450 mg/m² every two weeks; Drug: Leucovorin; d1 Leucovorin 200 mg/m² every two weeks; Drug: Oxaliplatin; d1 Oxaliplatin 85 mg/m² every two weeks; Drug: Docetaxel; d1 Docetaxel 50mg/m2 every two weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
median overall survival	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Disease free survival	2 years
Pathologic complete response rate	1 month after surgery
Perioperative Morbidity and Mortality	1 months after surgery
R0-Resection rate	1 month after surgery

Collaborators and Investigators

• Sponsor: Blokhin's Russian Cancer Research Center
• Investigators: Principal Investigator: Ivan Stilidi, PhD, NN Blokhin National Medical Research Center of Oncology

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2019
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): January 1, 2026

Study Registration Dates

• First Submitted: April 15, 2020
• First Submitted That Met QC Criteria: May 17, 2020
• First Posted (Actual): May 19, 2020

Study Record Updates

• Last Update Posted (Actual): April 13, 2021
• Last Update Submitted That Met QC Criteria: April 12, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: FLOT; gastric cancer; gastrectomy; adenocarcinoma of the stomach; FOLFIRINOX; pathological complete; adenocarcinoma of the esophagogastric junction
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Diseases; Stomach Diseases; Neoplasms; Stomach Neoplasms; Adenocarcinoma; Gastrointestinal Neoplasms; Digestive System Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Docetaxel; Oxaliplatin; Leucovorin; Irinotecan
• Other Study ID Numbers: 2019-01 (Other Identifier: NANT)

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