5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) Versus Epirubicin, Cisplatin and 5-FU (ECF) in Patients With Locally Advanced, Resectable Gastric Cancer

Krankenhaus Nordwest

Status and phase: Completed; Phase 3; Phase 2

Conditions: Gastric Cancer

Treatments: Drug: Docetaxel; Drug: Cisplatin; Drug: Epirubicin; Drug: Leucovorin; Drug: 5-Fluorouracil; Drug: Oxaliplatin; Drug: 5-fluorouracil

Study type: Interventional

Funder types: Other

Identifiers

NCT01216644

FLOT4

Details and patient eligibility

About

Patients with locally advanced resectable adenocarcinoma of the stomach or the esophagogastreal junction 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 Epirubicin, Cisplatin and 5-FU (ECF). Main objective of the study is median overall survival.

Full description

714 Patients with locally advanced resectable (T2-4 and/or N+, M0) adenocarcinoma of the stomach or the esophagogastreal junction without previous therapy will be included in this study. After randomization patients receive perioperatively 4 cycles FLOT or 3 cycles ECF, followed by a restaging of the tumour status and surgery. Subsequently another 4 cycles of FLOT or 3 cycles ECF are applicated. Then a central validation of the pathological remission rate is scheduled. Primary endpoint is overall survival, secondary endpoints are disease free survival, perioperative morbidity and mortality, histopathologic regression rate and R0-resection rate.

Enrollment: 716 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. locally advanced (>T1) and/or nodal positive (N+) histologically proven adenocarcinoma of the esophagogastreal junction (AEG I-III) or the stomach without distant metastases (M0) and without infiltration of adjacent structures and organs
2. no previous surgical resection
3. no previous cytostatic chemotherapy
4. Age > 18 years (female and male)
5. ECOG ≤ 2
6. surgical resectability
7. Exclusion of peritoneal carcinomatosis (if clinically suspected) via laparoscopy
8. Leucocytes > 3.000/µl
9. Platelets > 100.000/µl
10. Serum creatinin ≤ 1.5x of normal value, or Creatinin-Clearance > 50 ml/min
11. written informed consent.
12. Ejection fraction > 50% in echocardiography before start of therapy

Exclusion criteria

1. distant metastases or infiltration of adjacent structures or organs and all primarily not resectable stages
2. relapse
3. Hypersensitivity against 5- Fluorouracil, Leucovorin, Oxaliplatin, Cisplatin. Epirubicin and Docetaxel
4. Existence of contraindications against 5- Fluorouracil, Leucovorin, Oxaliplatin, Cisplatin, Epirubicin or Docetaxel
5. Active CHD, Cardiomyopathy or cardiac insufficiency stage III-IV according to NYHA
6. malignant secondary disease, dated back < 5 years (exception: In-situ-carcinoma of the cervix uteri, adequately treated skin basal cell carcinoma)
7. severe non-surgical accompanying disease or acute infection
8. peripheral polyneuropathy > NCI Grad II
9. severe liver dysfunction (AST/ALT>3,5xULN, AP>6xULN, Bilirubin>1,5xULN)
10. chronic inflammable gastro-intestinal disease
11. inclusion in another clinical trial
12. pregnancy or lactation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

716 participants in 2 patient groups

FLOT

Experimental group

Description:

Docetaxel 50mg/m2, d1 5-FU 2600 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m², d1 every two weeks (q2w) 4 cycles (8 weeks) pre-OP and 4 cycles (8 weeks) post-OP

Treatment:

Drug: Docetaxel

Drug: Oxaliplatin

Drug: Leucovorin

Drug: 5-Fluorouracil

ECF

Active Comparator group

Description:

Epirubicin 50 mg/m2, d1 Cisplatin 60 mg/m², d1 5-FU 200 mg/m², d1-d21 every 3 weeks (q3w) 3 cycles (9 weeks) pre-OP and 3 cycles (9 weeks) post-OP

Treatment:

Drug: 5-fluorouracil

Drug: Cisplatin

Drug: Epirubicin