Perioperative Chemotherapy Compared To Neoadjuvant Chemoradiation in Patients With Adenocarcinoma of the Esophagus
- Conditions
- Esophageal Adenocarcinoma (UICC TNM7)Adenocarcinoma of the Esophagogastric Junction
- Interventions
- Radiation: Neoadjuvant radiation
- Registration Number
- NCT02509286
- Lead Sponsor
- University Hospital Schleswig-Holstein
- 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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 438
Not provided
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Neoadjuvant Chemoradiation (CROSS): Neoadjuvant radiation 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. Perioperative Chemotherapy (FLOT): 5-Fluorouracil 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. Perioperative Chemotherapy (FLOT): Leucovorin 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. Perioperative Chemotherapy (FLOT): Oxaliplatin 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. Perioperative Chemotherapy (FLOT): Docetaxel 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. Neoadjuvant Chemoradiation (CROSS): Carboplatin 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. Neoadjuvant Chemoradiation (CROSS): Paclitaxel 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.
- Primary Outcome Measures
Name Time Method Overall survival 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
Name Time Method Non-surgical site complications From time of surgery up to 90 days postoperatively Recurrence free survival time 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 From randomization 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 Postoperative complications From time of surgery up to 90 days postoperatively Progression free survival time (PFS) 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.
Trial Locations
- Locations (30)
Ruppiner Kliniken GmbH
🇩🇪Neuruppin, Germany
Klinikum Dortmund gGmbH
🇩🇪Dortmund, Germany
Uniklinik Köln
🇩🇪Köln, Germany
Uniklinik RWTH Aachen
🇩🇪Aachen, Germany
Universitätsmedizin Mainz
🇩🇪Mainz, Germany
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universitätsklinikum Leipzig
🇩🇪Leipzig, Germany
Universitätsklinikum Erlangen
🇩🇪Erlangen, Germany
Universitätsklinikum Magdeburg
🇩🇪Magdeburg, Germany
Johannes Wesling Klinikum Minden
🇩🇪Minden, Germany
Universitätsklinikum Freiburg
🇩🇪Freiburg, Germany
Universitätsklinikum des Saarlandes
🇩🇪Homburg, Germany
Universitätsklinikum Schleswig-Holstein, Campus Lübeck
🇩🇪Lübeck, Germany
Universitätsklinikum Schleswig-Holstein, Campus Kiel
🇩🇪Kiel, Germany
Klinikum Stuttgart
🇩🇪Stuttgart, Germany
Charité Berlin Campus Virchow-Klinikum (CVK)
🇩🇪Berlin, Germany
Charité Berlin - Campus Benjamin Franklin (CBF)
🇩🇪Berlin, Germany
Universitätsklinikum Mannheim GmbH
🇩🇪Mannheim, Germany
Klinikum der Universität München (LMU)
🇩🇪München, Germany
Universitätsklinikum Münster
🇩🇪Münster, Germany
Universitätsklinikum Regensburg
🇩🇪Regensburg, Germany
Robert-Bosch-Krankenhaus Stuttgart
🇩🇪Stuttgart, Germany
Universitätsmedizin Rostock
🇩🇪Rostock, Germany
Klinikum Mutterhaus
🇩🇪Trier, Germany
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
🇩🇪Dresden, Germany
Universitätsmedizin Göttingen
🇩🇪Göttingen, Germany
Universitätsklinikum Düsseldorf
🇩🇪Düsseldorf, Germany
Universitätsklinikum Frankfurt
🇩🇪Frankfurt am Main, Germany
Sana Klinikum Offenbach GmbH
🇩🇪Offenbach, Germany
Universitätsklinikum Würzburg
🇩🇪Würzburg, Germany