Clinical trial NCT04393584: FOLFIRINOX vs FLOT Chemotherapy for Resectable Gastric or Esophagogastric Junction Adenocarcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Stomach Neoplasms
Gastrointestinal Neoplasms
Docetaxel
Oxaliplatin
Fluoruracil
Irinotecan Hydrochloride
Keywords: gastric cancer
pathological complete
FLOT
FOLFIRINOX
gastrectomy
adenocarcinoma of the esophagogastric junction
adenocarcinoma of the stomach
Lead sponsor: Blokhin's Russian Cancer Research Center
Sponsor class: OTHER
First posted: 2020-05-19
Enrollment: 538
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: median overall survival
timeFrame: 2 years
Secondary outcomes:
measure: Pathologic complete response rate
timeFrame: 1 month after surgery
measure: Disease free survival
timeFrame: 2 years
measure: Perioperative Morbidity and Mortality
timeFrame: 1 months after surgery
measure: R0-Resection rate
timeFrame: 1 month after surgery
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Aleksei Kalinin
Study officials:
affiliation: NN Blokhin National Medical Research Center of Oncology
name: Ivan Stilidi, PhD
role: PRINCIPAL_INVESTIGATOR
References: