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

Phase 2

Completed

• Conditions: Gastric Cancer
• Interventions: Drug: 5-fluorouracil; Drug: Epirubicin; Drug: Leucovorin; Drug: Cisplatin; Drug: Oxaliplatin; Drug: Docetaxel

• Registration Number: NCT01216644
• Lead Sponsor: Krankenhaus Nordwest

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2010-06-30
• Study Start: 2010-08
• Study First Submitted QC: 2010-10-06
• Study First Posted: 2010-10-07
• Primary Completion: 2017-03
• Study Completion: 2019-05
• Status Verified: 2019-06
• Last Update Submitted: 2019-06-18
• Last Update Posted: 2019-06-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 716

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FLOT	5-fluorouracil	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
FLOT	Leucovorin	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
ECF	Cisplatin	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
ECF	5-fluorouracil	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
FLOT	Oxaliplatin	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
FLOT	Docetaxel	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
ECF	Epirubicin	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

Primary Outcome Measures

Name	Time	Method
median overall survival	2 years follow-up

Secondary Outcome Measures

Name	Time	Method
correlation of pCR and DFS with survival	2 years follow-up
histopathological regression rate	6 weeks after surgery
R0-Resection rate	2 months after surgery
disease free survival (DFS)	2 years follow-up
Perioperative Morbidity and Mortality	up to 2 months after surgery

Trial Locations

Locations (1)

Krankenhaus Nordwest; 🇩🇪 Frankfurt, Germany