Clinical trial NCT02509286: Perioperative Chemotherapy Compared To Neoadjuvant Chemoradiation in Patients With Adenocarcinoma of the Esophagus
Official title: Perioperative Chemotherapy (FLOT Protocol) Compared To Neoadjuvant Chemoradiation (CROSS Protocol) in Patients With Adenocarcinoma of the Esophagus
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Esophageal Adenocarcinoma (UICC TNM7)
Adenocarcinoma of the Esophagogastric Junction
Keywords: Esophageal neoplasms
gastro-esophageal junction neoplasms
adenocarcinoma
esophagectomy
surgery
radiotherapy
chemotherapy
Lead sponsor: University Hospital Schleswig-Holstein
Sponsor class: OTHER
Collaborators: name: Clinical Trials Unit Freiburg
name: University of Freiburg
name: University of Leipzig
name: University of Luebeck
name: University of Hamburg-Eppendorf
First posted: 2015-07-28
Enrollment: 438
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival
timeFrame: At end of trial- up to 3 years in follow up
Secondary outcomes:
measure: Progression free survival time (PFS)
timeFrame: From randomisation up to 3 years in follow up
measure: Site of failure: local, regional or distant Failure
timeFrame: From time of surgery up to 3 years in follow up
measure: Recurrence free survival time
timeFrame: From time of surgery up to 3 years in follow up
measure: Postsurgical Quality of Life
timeFrame: From randomization up to 3 years in follow up
measure: Postoperative complications
timeFrame: From time of surgery up to 90 days postoperatively
measure: Non-surgical site complications
timeFrame: From time of surgery up to 90 days postoperatively
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Uniklinik RWTH Aachen
city: Berlin
country: Germany
facility: Charité Berlin - Campus Benjamin Franklin (CBF)
city: Berlin
country: Germany
facility: Charité Berlin Campus Virchow-Klinikum (CVK)
city: Dortmund
country: Germany
facility: Klinikum Dortmund gGmbH
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Kiel
city: Köln
country: Germany
facility: Uniklinik Köln
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Lübeck
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim GmbH
city: Minden
country: Germany
facility: Johannes Wesling Klinikum Minden
city: München
country: Germany
facility: Klinikum der Universität München (LMU)
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Neuruppin
country: Germany
facility: Ruppiner Kliniken GmbH
city: Offenbach
country: Germany
facility: Sana Klinikum Offenbach GmbH
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus Stuttgart
city: Trier
country: Germany
facility: Klinikum Mutterhaus
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
Study officials:
affiliation: University Medical Center Schleswig-Holstein, Campus Lübeck
name: Jens Hoeppner, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.