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

NCT01216644 | Completed Phase 2 DMC

• 1 other identifier: FLOT4
• Study Type: interventional
• Target: 716
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastric Cancer

Keywords

gastric cancer; perioperative; FLOT; ECF; pathological complete remission; locally advanced resectable adenocarcinoma of the esophagogastric juction or the stomach

Outcome Measures

Primary Outcomes (1)

• median overall survival

  2 years follow-up

Secondary Outcomes (5)

• histopathological regression rate

  6 weeks after surgery

• disease free survival (DFS)

  2 years follow-up

• correlation of pCR and DFS with survival

  2 years follow-up

• Perioperative Morbidity and Mortality

  up to 2 months after surgery

• R0-Resection rate

  2 months after surgery

Study Arms (2)

FLOT

EXPERIMENTAL

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; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Docetaxel

ECF

ACTIVE COMPARATOR

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; Drug: Cisplatin; Drug: 5-fluorouracil

Interventions

5-fluorouracil DRUG

2600 mg/m²d1 i.v. every 2 weeks

FLOT

Leucovorin DRUG

200 mg/m², d1, i.v., every 2 weeks

FLOT

Oxaliplatin DRUG

85 mg/m², d1, i.v., every 2 weeks

FLOT

Docetaxel DRUG

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

FLOT

Epirubicin DRUG

50 mg/m2, d1, i.v., every 3 weeks

ECF

Cisplatin DRUG

60 mg/m², d1, i.v., every 3 weeks

ECF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• no previous surgical resection
• no previous cytostatic chemotherapy
• Age \> 18 years (female and male)
• ECOG ≤ 2
• surgical resectability
• Leucocytes \> 3.000/µl
• Platelets \> 100.000/µl
• Serum creatinin ≤ 1.5x of normal value, or Creatinin-Clearance \> 50 ml/min
• written informed consent.
• Ejection fraction \> 50% in echocardiography before start of therapy

You may not qualify if:

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

Sponsors & Collaborators

• Krankenhaus Nordwest: lead

Study Sites (1)

Krankenhaus Nordwest

Frankfurt, 60488, Germany

Location

Related Publications (5)

• Zeng H, Wang C, Song LY, Jia SJ, Zeng X, Liu Q. Economic evaluation of FLOT and ECF/ECX perioperative chemotherapy in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma. BMJ Open. 2022 Nov 14;12(11):e060983. doi: 10.1136/bmjopen-2022-060983.

  PMID: 36375981 DERIVED

• Koch C, Reitz C, Schreckenbach T, Eichler K, Filmann N, Al-Batran SE, Gotze T, Zeuzem S, Bechstein WO, Kraus T, Bojunga J, Dux M, Trojan J, Blumenstein I. Sarcopenia as a prognostic factor for survival in patients with locally advanced gastroesophageal adenocarcinoma. PLoS One. 2019 Oct 22;14(10):e0223613. doi: 10.1371/journal.pone.0223613. eCollection 2019.

  PMID: 31639132 DERIVED

• 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.

  PMID: 30982686 DERIVED

• 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.

  PMID: 27776843 DERIVED

• Lorenzen S, Thuss-Patience P, Al-Batran SE, Lordick F, Haller B, Schuster T, Pauligk C, Luley K, Bichev D, Schumacher G, Homann N. Impact of pathologic complete response on disease-free survival in patients with esophagogastric adenocarcinoma receiving preoperative docetaxel-based chemotherapy. Ann Oncol. 2013 Aug;24(8):2068-73. doi: 10.1093/annonc/mdt141. Epub 2013 Apr 16.

  PMID: 23592699 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms; Pathologic Complete Response

Interventions

Fluorouracil; Leucovorin; Oxaliplatin; Docetaxel; Epirubicin; Cisplatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Salah-Eddin Al-Batran, MD

  Institute of Clinical Cancer Research (IKF), UCT - University Cancer Center, Frankfurt, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 30, 2010
• First Posted: October 7, 2010
• Study Start: August 1, 2010
• Primary Completion: March 1, 2017
• Study Completion: May 1, 2019
• Last Updated: June 19, 2019

Record last verified: 2019-06

Locations

DE (1)