Perioperative Chemotherapy Compared To Neoadjuvant Chemoradiation in Patients With Adenocarcinoma of the Esophagus

Adenocarcinoma of the Esophagogastric Junction Clinical Trial

— ESOPEC  

Official title:

Perioperative Chemotherapy (FLOT Protocol) Compared To Neoadjuvant Chemoradiation (CROSS Protocol) in Patients With Adenocarcinoma of the Esophagus

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02509286
• Other study ID #: P000760
• Secondary ID: 2015-001683-20DR
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 2016
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: University Hospital Schleswig-Holstein
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The trial is designed to investigate differences in outcome of patients with esophageal adenocarcinoma and junctional adenocarcinoma treated with perioperative (neoadjuvant + adjuvant) chemotherapy (FLOT) plus surgical resection versus neoadjuvant chemoradiation (CROSS) plus surgical resection.

Description:

According to the given evidence a survival benefit of perioperative chemotherapy (periCTX) over Neoadjuvant chemoradiation (neoCRT) for patients with Esophageal adenocarcinomas (EAC) has not been proven in any randomized controlled trials (RCT). Data supporting the value of periCTX have all been obtained in studies including mixed patient cohorts with EAC and gastric adenocarcinoma (GAC). Due to relevant differences of histologic subtype distribution, response to periCTX and survival rates between EAC and GAC there is a clear need to obtain evidence concerning the value of periCTX for EAC. As nowadays periCTX is extensively and successfully applied in clinical practice in patients with EAC there is an obvious need to obtain evidence from a multicentre RCT. Moreover a confirmation of the superior survival rates of the recent RCT on neoCRT should be obtained in a RCT conducted exclusively on EAC. Therefore, this prospective RCT with the primary objective of longterm patient survival comparing periCTX and neoCRT was designed.

Translational Projects:

Project 1+2: Circulating Tumor Cells as Biomarker in EAC CTC laboratories at University of Hamburg and University of Freiburg Project 3: Prognostic and predictive biomarkers in EAC University of Leipzig, UCCL

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 438
• Est. completion date: December 31, 2024
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Histologically verified adenocarcinoma of the esophagus according to the UICC definition (TNM7)

• Pre-treatment stage cT1N+, M0 or cT2-4a, N0/+, M0

• Age =18 years

• No prior abdominal or thoracic radiotherapy

• ECOG Performance status 0-2

• Adequate cardiac function ( Patients with a cardiac history (e.g. myocardial infarction, heart failure, coronary artery disease) should have a cardiology review)

• Adequate bone marrow function (WBC>3x10^9/l; Hb>9g/dl; platelets >100x10^9/l)

• Adequate respiratory function. Symptomatic Patients should have pulmonary function tests with FEV1 >65% of predicted)

• Adequate renal function (GFR >60ml/min)

• Adequate liver function (serum bilirubin <1.5x Upper level of Normal (ULN); AST <2.5x ULN and ALT <3x ULN (ULN as per institutional standard)

• written informed consent

Exclusion Criteria:

• Tumors of squamous or other non-adenocarcinoma histology

• Patients with advanced inoperable or metastatic esophageal adenocarcinoma

• Stage cT1N0 and cT4b

• Gastric carcinoma

• Prior chemotherapy for cancer,

• Clinically significant (i.e. active) cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within last 12 months)

• Clinical significant lung disease (FEV1 <65% of predicted)

• Peripheral neuropathy Grade >1

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Esophagogastric Junction
• Esophageal Adenocarcinoma (UICC TNM7)

Intervention

Drug:
• 5-Fluorouracil
2600 mg/m² (24 hours), d1 every two weeks;
• Leucovorin
200 mg/m² in 250 ml NaCl 0.9%, d1 every two weeks;
• Oxaliplatin
85 mg/m² in 500 ml G5% over 2h, d1 every two weeks;
• Docetaxel
50mg/m2 in 250 ml NaCl 0.9% over 1h, d1 every two weeks;
• Carboplatin
Dose-dependant: 2mg/ml/min AUC in 500ml Glucose 5%, day 1, 8, 15, 22 and day 29.
• Paclitaxel
50mg/m2 in 500ml NaCl 0.9% over 1 h, day 1, 8, 15, 22 and day 29;

Radiation:
• Neoadjuvant radiation
41.4Gy given in 23 fractions of 1.8Gy on days 1-5, days 8-12, days 15-19, days 22-26 and days 29-31.

Locations

Country	Name	City	State
Germany	Uniklinik RWTH Aachen	Aachen
Germany	Charité Berlin - Campus Benjamin Franklin (CBF)	Berlin
Germany	Charité Berlin Campus Virchow-Klinikum (CVK)	Berlin
Germany	Klinikum Dortmund gGmbH	Dortmund
Germany	Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden	Dresden
Germany	Universitätsklinikum Düsseldorf	Düsseldorf
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	Universitätsklinikum Frankfurt	Frankfurt am Main
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	Universitätsmedizin Göttingen	Göttingen
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitätsklinikum des Saarlandes	Homburg
Germany	Universitätsklinikum Schleswig-Holstein, Campus Kiel	Kiel
Germany	Uniklinik Köln	Köln
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Universitätsklinikum Schleswig-Holstein, Campus Lübeck	Lübeck
Germany	Universitätsklinikum Magdeburg	Magdeburg
Germany	Universitätsmedizin Mainz	Mainz
Germany	Universitätsklinikum Mannheim GmbH	Mannheim
Germany	Johannes Wesling Klinikum Minden	Minden
Germany	Klinikum der Universität München (LMU)	München
Germany	Universitätsklinikum Münster	Münster
Germany	Ruppiner Kliniken GmbH	Neuruppin
Germany	Sana Klinikum Offenbach GmbH	Offenbach
Germany	Universitätsklinikum Regensburg	Regensburg
Germany	Universitätsmedizin Rostock	Rostock
Germany	Klinikum Stuttgart	Stuttgart
Germany	Robert-Bosch-Krankenhaus Stuttgart	Stuttgart
Germany	Klinikum Mutterhaus	Trier
Germany	Universitätsklinikum Würzburg	Würzburg

Sponsors (6)

Lead Sponsor	Collaborator
University Hospital Schleswig-Holstein	Clinical Trials Unit Freiburg, University of Freiburg, University of Hamburg-Eppendorf, University of Leipzig, University of Luebeck

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Hoeppner J, Lordick F, Brunner T, Glatz T, Bronsert P, Rothling N, Schmoor C, Lorenz D, Ell C, Hopt UT, Siewert JR. ESOPEC: prospective randomized controlled multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (NCT02509286). BMC Cancer. 2016 Jul 19;16:503. doi: 10.1186/s12885-016-2564-y. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Overall survival will be calculated as time from start of study treatment to death due to any cause.	At end of trial- up to 3 years in follow up
Secondary	Progression free survival time (PFS)	PFS will be calculated as the time interval from randomisation to the first event of locoregional failure, metastatic progression or death.	From randomisation up to 3 years in follow up
Secondary	Site of failure: local, regional or distant Failure		From time of surgery up to 3 years in follow up
Secondary	Recurrence free survival time	RFS will be calculated in resected patients who achieved an R0 or R1 resection as the time interval from surgery to the date of first recurrence (local, regional or distant) or death, whatever comes first.	From time of surgery up to 3 years in follow up
Secondary	Postsurgical Quality of Life		From randomization up to 3 years in follow up
Secondary	Postoperative complications		From time of surgery up to 90 days postoperatively
Secondary	Non-surgical site complications		From time of surgery up to 90 days postoperatively

External Links

•   ESOPEC Homepage