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

NCT02509286 | Active Not Recruiting Phase 3 DMC

• 3 other identifiers: P0007602015-001683-20DRKS00008008
• Study Type: interventional
• Target: 438
• Locations: 1 country
• Sites: 30

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.

Conditions

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

Keywords

Esophageal neoplasms; gastro-esophageal junction neoplasms; adenocarcinoma; esophagectomy; surgery; radiotherapy; chemotherapy

Outcome Measures

Primary Outcomes (1)

• Overall survival

  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 Outcomes (6)

• Progression free survival time (PFS)

  From randomisation up to 3 years in follow up

• Site of failure: local, regional or distant Failure

  From time of surgery up to 3 years in follow up

• Recurrence free survival time

  From time of surgery up to 3 years in follow up

• Postsurgical Quality of Life

  From randomization up to 3 years in follow up

• Postoperative complications

  From time of surgery up to 90 days postoperatively

Study Arms (2)

Perioperative Chemotherapy (FLOT):

EXPERIMENTAL

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; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Docetaxel

Neoadjuvant Chemoradiation (CROSS):

ACTIVE COMPARATOR

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; Drug: Paclitaxel; Radiation: Neoadjuvant radiation

Interventions

5-Fluorouracil DRUG

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

Perioperative Chemotherapy (FLOT):

Leucovorin DRUG

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

Perioperative Chemotherapy (FLOT):

Oxaliplatin DRUG

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

Perioperative Chemotherapy (FLOT):

Docetaxel DRUG

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

Perioperative Chemotherapy (FLOT):

Carboplatin DRUG

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

Neoadjuvant Chemoradiation (CROSS):

Paclitaxel DRUG

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

Neoadjuvant Chemoradiation (CROSS):

Neoadjuvant radiation 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.

Neoadjuvant Chemoradiation (CROSS):

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Schleswig-Holstein: lead
• Clinical Trials Unit Freiburg: collaborator
• University of Freiburg: collaborator
• University of Leipzig: collaborator
• University of Luebeck: collaborator
• University of Hamburg-Eppendorf: collaborator

Study Sites (30)

Uniklinik RWTH Aachen

Aachen, Germany

Location

Charité Berlin - Campus Benjamin Franklin (CBF)

Berlin, 12203, Germany

Location

Charité Berlin Campus Virchow-Klinikum (CVK)

Berlin, 13353, Germany

Location

Uniklinik Köln

Cologne, 50937, Germany

Location

Klinikum Dortmund gGmbH

Dortmund, 44137, Germany

Location

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, 03107, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, Germany

Location

Universitätsklinikum Erlangen

Erlangen, 91054, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, 60590, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, Germany

Location

Universitätsmedizin Göttingen

Göttingen, 37099, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Germany

Location

Universitätsklinikum des Saarlandes

Homburg, 66421, Germany

Location

Universitätsklinikum Schleswig-Holstein, Campus Kiel

Kiel, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Germany

Location

Universitätsklinikum Schleswig-Holstein, Campus Lübeck

Lübeck, Germany

Location

Universitätsklinikum Magdeburg

Magdeburg, Germany

Location

Universitätsmedizin Mainz

Mainz, Germany

Location

Universitätsklinikum Mannheim GmbH

Mannheim, 68167, Germany

Location

Johannes Wesling Klinikum Minden

Minden, 32429, Germany

Location

Klinikum der Universität München (LMU)

München, Germany

Location

Universitätsklinikum Münster

Münster, Germany

Location

Ruppiner Kliniken GmbH

Neuruppin, 16816, Germany

Location

Sana Klinikum Offenbach GmbH

Offenbach, 63069, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

Universitätsmedizin Rostock

Rostock, 18059, Germany

Location

Klinikum Stuttgart

Stuttgart, 70174, Germany

Location

Robert-Bosch-Krankenhaus Stuttgart

Stuttgart, 70376, Germany

Location

Klinikum Mutterhaus

Trier, 54290, Germany

Location

Universitätsklinikum Würzburg

Würzburg, Germany

Location

Related Publications (2)

• 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.

  PMID: 27435280 BACKGROUND

• 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.

  PMID: 39842010 DERIVED

Related Links

• ESOPEC Homepage

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Esophageal Neoplasms; Adenocarcinoma

Interventions

Fluorouracil; Leucovorin; Oxaliplatin; Docetaxel; Carboplatin; Paclitaxel; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Combined Modality Therapy; Therapeutics

Study Officials

• Jens Hoeppner, Professor

  University Medical Center Schleswig-Holstein, Campus Lübeck

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Director - Department of Surgery

Study Record Dates

• First Submitted: July 22, 2015
• First Posted: July 28, 2015
• Study Start: January 1, 2016
• Primary Completion: May 1, 2024
• Study Completion: December 31, 2024
• Last Updated: May 8, 2024

Record last verified: 2024-05

Locations

DE (30)