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

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ClinicalTrials.gov Identifier: NCT02509286
Recruitment Status : Recruiting
First Posted : July 28, 2015
Last Update Posted : August 7, 2018
Sponsor:
Collaborators:
Clinical Trials Unit Freiburg
CTC laboratories at University of Hamburg and University of Freiburg
ESOPEC reference pathology at the University of Freiburg
Universitätsklinikum Leipzig, Universitäres Krebszentrum (UCCL)
Information provided by (Responsible Party):
Prof. Dr. Jens Hoeppner, University Hospital Freiburg

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.

Condition or disease Intervention/treatment Phase
Esophageal Adenocarcinoma (UICC TNM7) Adenocarcinoma of the Esophagogastric Junction Drug: 5-Fluorouracil Drug: Leucovorin Drug: Oxaliplatin Drug: Docetaxel Drug: Carboplatin Drug: Paclitaxel Radiation: Neoadjuvant radiation Phase 3

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 biomarkes in EAC University of Leipzig, UCCL

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 438 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Perioperative Chemotherapy (FLOT Protocol) Compared To Neoadjuvant Chemoradiation (CROSS Protocol) in Patients With Adenocarcinoma of the Esophagus
Study Start Date : January 2016
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. Site of failure: local, regional or distant Failure [ Time Frame: From time of surgery up to 3 years in follow up ]
  3. 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.

  4. Postsurgical Quality of Life [ Time Frame: From randomization up to 3 years in follow up ]
  5. Postoperative complications [ Time Frame: From time of surgery up to 90 days postoperatively ]
  6. Non-surgical site complications [ Time Frame: From time of surgery up to 90 days postoperatively ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02509286


Contacts
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Contact: Jens Hoeppner, Professor +49 761 270-26970 jens.hoeppner@uniklinik-freiburg.de

Locations
Show Show 29 study locations
Sponsors and Collaborators
University Hospital Freiburg
Clinical Trials Unit Freiburg
CTC laboratories at University of Hamburg and University of Freiburg
ESOPEC reference pathology at the University of Freiburg
Universitätsklinikum Leipzig, Universitäres Krebszentrum (UCCL)
Investigators
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Principal Investigator: Jens Hoeppner, Professor University Hospital Freiburg

Additional Information:
Publications:
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Responsible Party: Prof. Dr. Jens Hoeppner, Head of Upper GI Surgery Programm, University Hospital Freiburg
ClinicalTrials.gov Identifier: NCT02509286    
Other Study ID Numbers: P000760
2015-001683-20 ( EudraCT Number )
DRKS00008008 ( Registry Identifier: DRKS )
First Posted: July 28, 2015    Key Record Dates
Last Update Posted: August 7, 2018
Last Verified: July 2018
Keywords provided by Prof. Dr. Jens Hoeppner, University Hospital Freiburg:
Esophageal neoplasms
gastro-esophageal junction neoplasms
adenocarcinoma
esophagectomy
surgery
radiotherapy
chemotherapy
Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Paclitaxel
Docetaxel
Carboplatin
Oxaliplatin
Fluorouracil
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs