FOLFIRINOX vs FLOT Chemotherapy for Resectable Gastric or Esophagogastric Junction Adenocarcinoma

Phase 2

Recruiting

• Conditions: Stomach Neoplasms; Gastrointestinal Neoplasms; Docetaxel; Oxaliplatin; Fluoruracil; Irinotecan Hydrochloride
• Interventions: Drug: Irinotecan; Drug: 5-FU; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Docetaxel

• Registration Number: NCT04393584
• Lead Sponsor: Blokhin's Russian Cancer Research Center

Brief Summary

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.

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 Timeline

• Study Start: 2019-01-29
• Study First Submitted: 2020-04-15
• Study First Submitted QC: 2020-05-17
• Study First Posted: 2020-05-19
• Status Verified: 2021-04
• Last Update Submitted: 2021-04-12
• Last Update Posted: 2021-04-13
• Primary Completion: 2024-01-01
• Study Completion: 2026-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 538

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FOLFIRINOX	Oxaliplatin	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
FLOT	Oxaliplatin	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
FLOT	Docetaxel	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
FOLFIRINOX	Irinotecan	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
FOLFIRINOX	Leucovorin	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
FOLFIRINOX	5-FU	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
FLOT	5-FU	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
FLOT	Leucovorin	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

Primary Outcome Measures

Name	Time	Method
median overall survival	2 years

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Aleksei Kalinin; 🇷🇺 Moscow, Russian Federation