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

May 7, 2024 updated by: Jens Hoeppner, University Hospital Schleswig-Holstein

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
438

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Aachen, Germany
        • Uniklinik RWTH Aachen
      • Berlin, Germany, 12203
        • Charité Berlin - Campus Benjamin Franklin (CBF)
      • Berlin, Germany, 13353
        • Charité Berlin Campus Virchow-Klinikum (CVK)
      • Dortmund, Germany, 44137
        • Klinikum Dortmund gGmbH
      • Dresden, Germany, 03107
        • Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden
      • Düsseldorf, Germany
        • Universitätsklinikum Düsseldorf
      • Erlangen, Germany, 91054
        • Universitätsklinikum Erlangen
      • Frankfurt am Main, Germany, 60590
        • Universitätsklinikum Frankfurt
      • Freiburg, Germany
        • Universitätsklinikum Freiburg
      • Göttingen, Germany, 37099
        • Universitätsmedizin Göttingen
      • Hamburg, Germany
        • Universitätsklinikum Hamburg-Eppendorf
      • Homburg, Germany, 66421
        • Universitätsklinikum des Saarlandes
      • Kiel, Germany
        • Universitätsklinikum Schleswig-Holstein, Campus Kiel
      • Köln, Germany, 50937
        • Uniklinik Köln
      • Leipzig, Germany
        • Universitatsklinikum Leipzig
      • Lübeck, Germany
        • Universitätsklinikum Schleswig-Holstein, Campus Lübeck
      • Magdeburg, Germany
        • Universitätsklinikum Magdeburg
      • Mainz, Germany
        • Universitätsmedizin Mainz
      • Mannheim, Germany, 68167
        • Universitätsklinikum Mannheim GmbH
      • Minden, Germany, 32429
        • Johannes Wesling Klinikum Minden
      • München, Germany
        • Klinikum der Universität München (LMU)
      • Münster, Germany
        • Universitatsklinikum Munster
      • Neuruppin, Germany, 16816
        • Ruppiner Kliniken GmbH
      • Offenbach, Germany, 63069
        • Sana Klinikum Offenbach GmbH
      • Regensburg, Germany, 93053
        • Universitatsklinikum Regensburg
      • Rostock, Germany, 18059
        • Universitatsmedizin Rostock
      • Stuttgart, Germany, 70174
        • Klinikum Stuttgart
      • Stuttgart, Germany, 70376
        • Robert-Bosch-Krankenhaus Stuttgart
      • Trier, Germany, 54290
        • Klinikum Mutterhaus
      • Würzburg, Germany
        • Universitätsklinikum Würzburg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Perioperative Chemotherapy (FLOT):

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.
Drug: 5-Fluorouracil
2600 mg/m² (24 hours), d1 every two weeks;
Drug: Leucovorin
200 mg/m² in 250 ml NaCl 0.9%, d1 every two weeks;
Drug: Oxaliplatin
85 mg/m² in 500 ml G5% over 2h, d1 every two weeks;
Drug: Docetaxel
50mg/m2 in 250 ml NaCl 0.9% over 1h, d1 every two weeks;
Active Comparator: Neoadjuvant Chemoradiation (CROSS):

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.
Drug: Carboplatin
Dose-dependant: 2mg/ml/min AUC in 500ml Glucose 5%, day 1, 8, 15, 22 and day 29.
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: At end of trial- up to 3 years in follow up
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression free survival time (PFS)
Time Frame: From randomisation up to 3 years in follow up
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
Site of failure: local, regional or distant Failure
Time Frame: From time of surgery up to 3 years in follow up
From time of surgery up to 3 years in follow up
Recurrence free survival time
Time Frame: From time of surgery up to 3 years in follow up
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
Postsurgical Quality of Life
Time Frame: From randomization up to 3 years in follow up
From randomization up to 3 years in follow up
Postoperative complications
Time Frame: From time of surgery up to 90 days postoperatively
From time of surgery up to 90 days postoperatively
Non-surgical site complications
Time Frame: From time of surgery up to 90 days postoperatively
From time of surgery up to 90 days postoperatively

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital Schleswig-Holstein

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Leipzig
University of Luebeck
University of Hamburg-Eppendorf
University of Freiburg
Clinical Trials Unit Freiburg

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jens Hoeppner, Professor, University Medical Center Schleswig-Holstein, Campus Lübeck

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2016

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 22, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 23, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 28, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 8, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 7, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P000760
  • 2015-001683-20 (EudraCT Number)
  • DRKS00008008 (Registry Identifier: DRKS)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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