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

Primary Purpose

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

Status
Active
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
5-Fluorouracil
Leucovorin
Oxaliplatin
Docetaxel
Carboplatin
Paclitaxel
Neoadjuvant radiation
Sponsored by
University Hospital Schleswig-Holstein
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Adenocarcinoma (UICC TNM7) focused on measuring Esophageal neoplasms, gastro-esophageal junction neoplasms, adenocarcinoma, esophagectomy, surgery, radiotherapy, chemotherapy

Eligibility Criteria

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

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Perioperative Chemotherapy (FLOT):

Neoadjuvant Chemoradiation (CROSS):

Arm Description

The FLOT Arm consists of the FLOT protocol, which consists of 5-Fluorouracil, Leucovorin, Oxaliplatin and Docetaxel. Repetition every 2 weeks (d15, q2w). Four neoadjuvant cycles (8 weeks) prior to surgery and four adjuvant cycles (8 weeks) postoperatively are given. Surgery is carried out by transthoracic subtotal esophagectomy or by transabdominal distal esophageal resection plus gastrectomy depending on tumor localization.

The CROSS Arm consists of the CROSS protocol, which consists of neoadjuvant radiation therapy (41.4Gy / 23fractions) and concurrent chemotherapy with Carboplatin and Paclitaxel (5 weeks) prior to surgery. Surgery is carried out by transthoracic subtotal esophagectomy or by transabdominal distal esophageal resection plus gastrectomy depending on tumor localization.

Outcomes

Primary Outcome Measures

Overall survival
Overall survival will be calculated as time from start of study treatment to death due to any cause.

Secondary Outcome Measures

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.
Site of failure: local, regional or distant Failure
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.
Postsurgical Quality of Life
Postoperative complications
Non-surgical site complications

Full Information

First Posted
July 22, 2015
Last Updated
November 1, 2022
Sponsor
University Hospital Schleswig-Holstein
Collaborators
Clinical Trials Unit Freiburg, University of Freiburg, University of Leipzig, University of Luebeck, University of Hamburg-Eppendorf
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1. Study Identification

Unique Protocol Identification Number
NCT02509286
Brief Title
Perioperative Chemotherapy Compared To Neoadjuvant Chemoradiation in Patients With Adenocarcinoma of the Esophagus
Acronym
ESOPEC
Official Title
Perioperative Chemotherapy (FLOT Protocol) Compared To Neoadjuvant Chemoradiation (CROSS Protocol) in Patients With Adenocarcinoma of the Esophagus
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 2016 (undefined)
Primary Completion Date
April 2023 (Anticipated)
Study Completion Date
June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital Schleswig-Holstein
Collaborators
Clinical Trials Unit Freiburg, University of Freiburg, University of Leipzig, University of Luebeck, University of Hamburg-Eppendorf

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Adenocarcinoma (UICC TNM7), Adenocarcinoma of the Esophagogastric Junction
Keywords
Esophageal neoplasms, gastro-esophageal junction neoplasms, adenocarcinoma, esophagectomy, surgery, radiotherapy, chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
438 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Perioperative Chemotherapy (FLOT):
Arm Type
Experimental
Arm Description
The FLOT Arm consists of the FLOT protocol, which consists of 5-Fluorouracil, Leucovorin, Oxaliplatin and Docetaxel. Repetition every 2 weeks (d15, q2w). Four neoadjuvant cycles (8 weeks) prior to surgery and four adjuvant cycles (8 weeks) postoperatively are given. Surgery is carried out by transthoracic subtotal esophagectomy or by transabdominal distal esophageal resection plus gastrectomy depending on tumor localization.
Arm Title
Neoadjuvant Chemoradiation (CROSS):
Arm Type
Active Comparator
Arm Description
The CROSS Arm consists of the CROSS protocol, which consists of neoadjuvant radiation therapy (41.4Gy / 23fractions) and concurrent chemotherapy with Carboplatin and Paclitaxel (5 weeks) prior to surgery. Surgery is carried out by transthoracic subtotal esophagectomy or by transabdominal distal esophageal resection plus gastrectomy depending on tumor localization.
Intervention Type
Drug
Intervention Name(s)
5-Fluorouracil
Intervention Description
2600 mg/m² (24 hours), d1 every two weeks;
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Intervention Description
200 mg/m² in 250 ml NaCl 0.9%, d1 every two weeks;
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
85 mg/m² in 500 ml G5% over 2h, d1 every two weeks;
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Intervention Description
50mg/m2 in 250 ml NaCl 0.9% over 1h, d1 every two weeks;
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Dose-dependant: 2mg/ml/min AUC in 500ml Glucose 5%, day 1, 8, 15, 22 and day 29.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
50mg/m2 in 500ml NaCl 0.9% over 1 h, day 1, 8, 15, 22 and day 29;
Intervention Type
Radiation
Intervention Name(s)
Neoadjuvant radiation
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall survival
Description
Overall survival will be calculated as time from start of study treatment to death due to any cause.
Time Frame
At end of trial- up to 3 years in follow up
Secondary Outcome Measure Information:
Title
Progression free survival time (PFS)
Description
PFS will be calculated as the time interval from randomisation to the first event of locoregional failure, metastatic progression or death.
Time Frame
From randomisation up to 3 years in follow up
Title
Site of failure: local, regional or distant Failure
Time Frame
From time of surgery up to 3 years in follow up
Title
Recurrence free survival time
Description
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.
Time Frame
From time of surgery up to 3 years in follow up
Title
Postsurgical Quality of Life
Time Frame
From randomization up to 3 years in follow up
Title
Postoperative complications
Time Frame
From time of surgery up to 90 days postoperatively
Title
Non-surgical site complications
Time Frame
From time of surgery up to 90 days postoperatively

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jens Hoeppner, Professor
Organizational Affiliation
University Medical Center Schleswig-Holstein, Campus Lübeck
Official's Role
Principal Investigator
Facility Information:
Facility Name
Uniklinik RWTH Aachen
City
Aachen
Country
Germany
Facility Name
Charité Berlin - Campus Benjamin Franklin (CBF)
City
Berlin
ZIP/Postal Code
12203
Country
Germany
Facility Name
Charité Berlin Campus Virchow-Klinikum (CVK)
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Klinikum Dortmund gGmbH
City
Dortmund
ZIP/Postal Code
44137
Country
Germany
Facility Name
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
City
Dresden
ZIP/Postal Code
03107
Country
Germany
Facility Name
Universitätsklinikum Düsseldorf
City
Düsseldorf
Country
Germany
Facility Name
Universitätsklinikum Erlangen
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Universitätsklinikum Frankfurt
City
Frankfurt am Main
ZIP/Postal Code
60590
Country
Germany
Facility Name
Universitätsklinikum Freiburg
City
Freiburg
Country
Germany
Facility Name
Universitätsmedizin Göttingen
City
Göttingen
ZIP/Postal Code
37099
Country
Germany
Facility Name
Universitätsklinikum Hamburg-Eppendorf
City
Hamburg
Country
Germany
Facility Name
Universitätsklinikum des Saarlandes
City
Homburg
ZIP/Postal Code
66421
Country
Germany
Facility Name
Universitätsklinikum Schleswig-Holstein, Campus Kiel
City
Kiel
Country
Germany
Facility Name
Uniklinik Köln
City
Köln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Universitätsklinikum Leipzig
City
Leipzig
Country
Germany
Facility Name
Universitätsklinikum Schleswig-Holstein, Campus Lübeck
City
Lübeck
Country
Germany
Facility Name
Universitätsklinikum Magdeburg
City
Magdeburg
Country
Germany
Facility Name
Universitätsmedizin Mainz
City
Mainz
Country
Germany
Facility Name
Universitätsklinikum Mannheim GmbH
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
Facility Name
Johannes Wesling Klinikum Minden
City
Minden
ZIP/Postal Code
32429
Country
Germany
Facility Name
Klinikum der Universität München (LMU)
City
München
Country
Germany
Facility Name
Universitätsklinikum Münster
City
Münster
Country
Germany
Facility Name
Ruppiner Kliniken GmbH
City
Neuruppin
ZIP/Postal Code
16816
Country
Germany
Facility Name
Sana Klinikum Offenbach GmbH
City
Offenbach
ZIP/Postal Code
63069
Country
Germany
Facility Name
Universitätsklinikum Regensburg
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Facility Name
Universitätsmedizin Rostock
City
Rostock
ZIP/Postal Code
18059
Country
Germany
Facility Name
Klinikum Stuttgart
City
Stuttgart
ZIP/Postal Code
70174
Country
Germany
Facility Name
Robert-Bosch-Krankenhaus Stuttgart
City
Stuttgart
ZIP/Postal Code
70376
Country
Germany
Facility Name
Klinikum Mutterhaus
City
Trier
ZIP/Postal Code
54290
Country
Germany
Facility Name
Universitätsklinikum Würzburg
City
Würzburg
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
27435280
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.
Results Reference
background
Links:
URL
https://www.uniklinik-freiburg.de/esopec-studie.html
Description
ESOPEC Homepage

Learn more about this trial

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

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