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

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ClinicalTrials.gov Identifier: NCT01216644
Recruitment Status : Completed
First Posted : October 7, 2010
Last Update Posted : June 19, 2019
Information provided by (Responsible Party):
Prof. Dr. S.E. Al-Batran, 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.

Condition or disease Intervention/treatment Phase
Gastric Cancer Drug: 5-Fluorouracil Drug: Leucovorin Drug: Oxaliplatin Drug: Docetaxel Drug: Epirubicin Drug: Cisplatin Drug: 5-fluorouracil Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 716 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Multicenter Phase II/III Study Comparing 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) Versus Epirubicin, Cisplatin and 5-FU (ECF) in Patients With Locally Advanced Resectable Adenocarcinoma of the Esophagogastreal Junction or the Stomach
Actual Study Start Date : August 2010
Actual Primary Completion Date : March 2017
Actual Study Completion Date : May 2019

Arm Intervention/treatment
Experimental: FLOT
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
Drug: 5-Fluorouracil
2600 mg/m²d1 i.v. every 2 weeks

Drug: Leucovorin
200 mg/m², d1, i.v., every 2 weeks

Drug: Oxaliplatin
85 mg/m², d1, i.v., every 2 weeks

Drug: Docetaxel
50mg/m2, d1, i.v., every 2 weeks

Active Comparator: ECF
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
Drug: Epirubicin
50 mg/m2, d1, i.v., every 3 weeks

Drug: Cisplatin
60 mg/m², d1, i.v., every 3 weeks

Drug: 5-fluorouracil
200 mg/m², d1-d21, i.v., every 3 weeks

Primary Outcome Measures :
  1. median overall survival [ Time Frame: 2 years follow-up ]

Secondary Outcome Measures :
  1. histopathological regression rate [ Time Frame: 6 weeks after surgery ]
  2. disease free survival (DFS) [ Time Frame: 2 years follow-up ]
  3. correlation of pCR and DFS with survival [ Time Frame: 2 years follow-up ]
  4. Perioperative Morbidity and Mortality [ Time Frame: up to 2 months after surgery ]
  5. R0-Resection rate [ Time Frame: 2 months after surgery ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01216644

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Krankenhaus Nordwest
Frankfurt, Germany, 60488
Sponsors and Collaborators
Krankenhaus Nordwest
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Principal Investigator: Salah-Eddin Al-Batran, MD Institute of Clinical Cancer Research (IKF), UCT - University Cancer Center, Frankfurt, Germany
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Lohr C, Bernhard H, Schuch G, Rethwisch V, von Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Weniger J, Belle S, Gaiser T, Oduncu FS, Guntner M, Hozaeel W, Reichart A, Jager E, Kraus T, Monig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019 May 11;393(10184):1948-1957. doi: 10.1016/S0140-6736(18)32557-1. Epub 2019 Apr 11.
Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, Meiler J, Homann N, Lorenzen S, Schmalenberg H, Probst S, Koenigsmann M, Egger M, Prasnikar N, Caca K, Trojan J, Martens UM, Block A, Fischbach W, Mahlberg R, Clemens M, Illerhaus G, Zirlik K, Behringer DM, Schmiegel W, Pohl M, Heike M, Ronellenfitsch U, Schuler M, Bechstein WO, Konigsrainer A, Gaiser T, Schirmacher P, Hozaeel W, Reichart A, Goetze TO, Sievert M, Jager E, Monig S, Tannapfel A. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016 Dec;17(12):1697-1708. doi: 10.1016/S1470-2045(16)30531-9. Epub 2016 Oct 22.

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Responsible Party: Prof. Dr. S.E. Al-Batran, Principal Investigator, Krankenhaus Nordwest
ClinicalTrials.gov Identifier: NCT01216644    
Other Study ID Numbers: FLOT4
First Posted: October 7, 2010    Key Record Dates
Last Update Posted: June 19, 2019
Last Verified: June 2019
Keywords provided by Prof. Dr. S.E. Al-Batran, Krankenhaus Nordwest:
gastric cancer
pathological complete remission
locally advanced resectable adenocarcinoma of the esophagogastric juction or the stomach
Additional relevant MeSH terms:
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Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protective Agents
Vitamin B Complex
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors