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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

Tracking Information
First Submitted Date  ICMJE July 22, 2015
First Posted Date  ICMJE July 28, 2015
Last Update Posted Date August 7, 2018
Study Start Date  ICMJE January 2016
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 2, 2015)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 23, 2015)
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. For patients alive at study end, the survival time will be censored at time of last known survival status.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2015)
  • 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.
  • Site of failure: local, regional or distant Failure [ Time Frame: 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.
  • Postsurgical Quality of Life [ Time Frame: From randomization up to 3 years in follow up ]
  • Postoperative complications [ Time Frame: From time of surgery up to 90 days postoperatively ]
  • Non-surgical site complications [ Time Frame: From time of surgery up to 90 days postoperatively ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Perioperative Chemotherapy Compared To Neoadjuvant Chemoradiation in Patients With Adenocarcinoma of the Esophagus
Official Title  ICMJE Perioperative Chemotherapy (FLOT Protocol) Compared To Neoadjuvant Chemoradiation (CROSS Protocol) in Patients With Adenocarcinoma of the Esophagus
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 biomarkes in EAC University of Leipzig, UCCL

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Esophageal Adenocarcinoma (UICC TNM7)
  • Adenocarcinoma of the Esophagogastric Junction
Intervention  ICMJE
  • 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;
  • 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.
Study Arms  ICMJE
  • 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.

    Interventions:
    • Drug: 5-Fluorouracil
    • Drug: Leucovorin
    • Drug: Oxaliplatin
    • Drug: Docetaxel
  • 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.

    Interventions:
    • Drug: Carboplatin
    • Drug: Paclitaxel
    • Radiation: Neoadjuvant radiation
Publications * Hoeppner J, Lordick F, Brunner T, Glatz T, Bronsert P, Röthling 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 23, 2015)
438
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jens Hoeppner, Professor +49 761 270-26970 jens.hoeppner@uniklinik-freiburg.de
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02509286
Other Study ID Numbers  ICMJE P000760
2015-001683-20 ( EudraCT Number )
DRKS00008008 ( Registry Identifier: DRKS )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Prof. Dr. Jens Hoeppner, University Hospital Freiburg
Study Sponsor  ICMJE University Hospital Freiburg
Collaborators  ICMJE
  • 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  ICMJE
Principal Investigator: Jens Hoeppner, Professor University Hospital Freiburg
PRS Account University Hospital Freiburg
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP