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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

Primary Purpose

Gastric Cancer

Status

Completed

Phase

Phase 2

Locations

Germany

Study Type

Interventional

Intervention

5-Fluorouracil

Leucovorin

Oxaliplatin

Docetaxel

Epirubicin

Cisplatin

5-fluorouracil

About this trial

This is an interventional treatment trial for Gastric Cancer focused on measuring gastric cancer, perioperative, FLOT, ECF, pathological complete remission, locally advanced resectable adenocarcinoma of the esophagogastric juction or the stomach

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
Exclusion of peritoneal carcinomatosis (if clinically suspected) via laparoscopy
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

Exclusion Criteria:

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
inclusion in another clinical trial
pregnancy or lactation

Sites / Locations

Krankenhaus Nordwest

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

FLOT

ECF

Arm 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

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

Outcomes

Primary Outcome Measures

median overall survival

Secondary Outcome Measures

histopathological regression rate

disease free survival (DFS)

correlation of pCR and DFS with survival

Perioperative Morbidity and Mortality

R0-Resection rate

Full Information

NCT ID

NCT01216644

First Posted

June 30, 2010

Last Updated

June 18, 2019

Sponsor

Krankenhaus Nordwest

1. Study Identification

Unique Protocol Identification Number

NCT01216644

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Completed

Study Start Date

August 2010 (Actual)

Primary Completion Date

March 2017 (Actual)

Study Completion Date

May 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Krankenhaus Nordwest

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastric Cancer

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

716 (Actual)

8. Arms, Groups, and Interventions

Arm Title

FLOT

Arm Type

Experimental

Arm 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

Arm Title

ECF

Arm Type

Active Comparator

Arm 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

Intervention Type

Drug

Intervention Name(s)

5-Fluorouracil

Intervention Description

2600 mg/m²d1 i.v. every 2 weeks

Intervention Type

Drug

Intervention Name(s)

Leucovorin

Intervention Description

200 mg/m², d1, i.v., every 2 weeks

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin

Intervention Description

85 mg/m², d1, i.v., every 2 weeks

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Epirubicin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Description

60 mg/m², d1, i.v., every 3 weeks

Intervention Type

Drug

Intervention Name(s)

5-fluorouracil

Intervention Description

200 mg/m², d1-d21, i.v., every 3 weeks

Primary Outcome Measure Information:

Title

median overall survival

Time Frame

2 years follow-up

Secondary Outcome Measure Information:

Title

histopathological regression rate

Time Frame

6 weeks after surgery

Title

disease free survival (DFS)

Time Frame

2 years follow-up

Title

correlation of pCR and DFS with survival

Time Frame

2 years follow-up

Title

Perioperative Morbidity and Mortality

Time Frame

up to 2 months after surgery

Title

R0-Resection rate

Time Frame

2 months after surgery

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion of peritoneal carcinomatosis (if clinically suspected) via laparoscopy 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 Exclusion Criteria: 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 inclusion in another clinical trial pregnancy or lactation

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Salah-Eddin Al-Batran, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

Krankenhaus Nordwest

City

Frankfurt

ZIP/Postal Code

60488

Country

Germany

12. IPD Sharing Statement

Citations:

PubMed Identifier

36375981

Citation

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.

Results Reference

derived

PubMed Identifier

31639132

Citation

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.

Results Reference

derived

PubMed Identifier

30982686

Citation

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.

Results Reference

derived

PubMed Identifier

27776843

Citation

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.

Results Reference

derived

PubMed Identifier

23592699

Citation

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.

Results Reference

derived

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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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