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

University Hospital Schleswig-Holstein (UKSH)

Status and phase: Active, not recruiting; Phase 3

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

Treatments: Radiation: Neoadjuvant radiation; Drug: Leucovorin; Drug: 5-Fluorouracil; Drug: Paclitaxel; Drug: Docetaxel; Drug: Carboplatin; Drug: Oxaliplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT02509286

2015-001683-20 (EudraCT Number)

DRKS00008008 (Registry Identifier)

P000760

Details and patient eligibility

About

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.

Full 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

Enrollment: 438 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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438 participants in 2 patient groups

Perioperative Chemotherapy (FLOT):

Experimental group

Description:

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.

Treatment:

Drug: Leucovorin

Drug: 5-Fluorouracil

Drug: Docetaxel

Drug: Oxaliplatin

Neoadjuvant Chemoradiation (CROSS):

Active Comparator group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Carboplatin

Radiation: Neoadjuvant radiation