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

NCT ID: NCT02509286

Last Updated: 2024-05-08

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 438 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2024-12-31

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

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

5-Fluorouracil

Intervention Type: DRUG

2600 mg/m² (24 hours), d1 every two weeks;

Leucovorin

Intervention Type: DRUG

200 mg/m² in 250 ml NaCl 0.9%, d1 every two weeks;

Oxaliplatin

Intervention Type: DRUG

85 mg/m² in 500 ml G5% over 2h, d1 every two weeks;

Docetaxel

Intervention Type: DRUG

50mg/m2 in 250 ml NaCl 0.9% over 1h, d1 every two weeks;

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.

Group Type: ACTIVE_COMPARATOR

Carboplatin

Intervention Type: DRUG

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

Paclitaxel

Intervention Type: DRUG

50mg/m2 in 500ml NaCl 0.9% over 1 h, day 1, 8, 15, 22 and day 29;

Neoadjuvant radiation

Intervention Type: 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.

Interventions

5-Fluorouracil

2600 mg/m² (24 hours), d1 every two weeks;

Intervention Type: DRUG

Leucovorin

200 mg/m² in 250 ml NaCl 0.9%, d1 every two weeks;

Intervention Type: DRUG

Oxaliplatin

85 mg/m² in 500 ml G5% over 2h, d1 every two weeks;

Intervention Type: DRUG

Docetaxel

50mg/m2 in 250 ml NaCl 0.9% over 1h, d1 every two weeks;

Intervention Type: DRUG

Carboplatin

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

Intervention Type: DRUG

Paclitaxel

50mg/m2 in 500ml NaCl 0.9% over 1 h, day 1, 8, 15, 22 and day 29;

Intervention Type: DRUG

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.

Intervention Type: RADIATION

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clinical Trials Unit Freiburg

OTHER

Sponsor Role: collaborator

University of Freiburg

OTHER

Sponsor Role: collaborator

University of Leipzig

OTHER

Sponsor Role: collaborator

University of Luebeck

OTHER

Sponsor Role: collaborator

University of Hamburg-Eppendorf

OTHER

Sponsor Role: collaborator

University Hospital Schleswig-Holstein

OTHER

Sponsor Role: lead

Responsible Party

Jens Hoeppner

Deputy Director - Department of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jens Hoeppner, Professor

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Schleswig-Holstein, Campus Lübeck

Locations

Uniklinik RWTH Aachen

Aachen, , Germany

Charité Berlin - Campus Benjamin Franklin (CBF)

Berlin, , Germany

Charité Berlin Campus Virchow-Klinikum (CVK)

Berlin, , Germany

Uniklinik Köln

Cologne, , Germany

Klinikum Dortmund gGmbH

Dortmund, , Germany

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, , Germany

Universitätsklinikum Düsseldorf

Düsseldorf, , Germany

Universitätsklinikum Erlangen

Erlangen, , Germany

Universitätsklinikum Frankfurt

Frankfurt am Main, , Germany

Universitätsklinikum Freiburg

Freiburg im Breisgau, , Germany

Universitätsmedizin Göttingen

Göttingen, , Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Universitätsklinikum des Saarlandes

Homburg, , Germany

Universitätsklinikum Schleswig-Holstein, Campus Kiel

Kiel, , Germany

Universitätsklinikum Leipzig

Leipzig, , Germany

Universitätsklinikum Schleswig-Holstein, Campus Lübeck

Lübeck, , Germany

Universitätsklinikum Magdeburg

Magdeburg, , Germany

Universitätsmedizin Mainz

Mainz, , Germany

Universitätsklinikum Mannheim GmbH

Mannheim, , Germany

Johannes Wesling Klinikum Minden

Minden, , Germany

Klinikum der Universität München (LMU)

München, , Germany

Universitätsklinikum Münster

Münster, , Germany

Ruppiner Kliniken GmbH

Neuruppin, , Germany

Sana Klinikum Offenbach GmbH

Offenbach, , Germany

Universitätsklinikum Regensburg

Regensburg, , Germany

Universitätsmedizin Rostock

Rostock, , Germany

Klinikum Stuttgart

Stuttgart, , Germany

Robert-Bosch-Krankenhaus Stuttgart

Stuttgart, , Germany

Klinikum Mutterhaus

Trier, , Germany

Universitätsklinikum Würzburg

Würzburg, , Germany

Countries

Germany

References

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.

Reference Type: BACKGROUND

PMID: 27435280 (View on PubMed)

Hoeppner J, Brunner T, Schmoor C, Bronsert P, Kulemann B, Claus R, Utzolino S, Izbicki JR, Gockel I, Gerdes B, Ghadimi M, Reichert B, Lock JF, Bruns C, Reitsamer E, Schmeding M, Benedix F, Keck T, Folprecht G, Thuss-Patience P, Neumann UP, Pascher A, Imhof D, Daum S, Strieder T, Krautz C, Zimmermann S, Werner J, Mahlberg R, Illerhaus G, Grimminger P, Lordick F. Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer. N Engl J Med. 2025 Jan 23;392(4):323-335. doi: 10.1056/NEJMoa2409408.

Reference Type: DERIVED

PMID: 39842010 (View on PubMed)

Related Links

https://www.uniklinik-freiburg.de/esopec-studie.html

ESOPEC Homepage

Other Identifiers

2015-001683-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DRKS00008008

Identifier Type: REGISTRY

Identifier Source: secondary_id

P000760

Identifier Type: -

Identifier Source: org_study_id