Adenocarcinoma of the Esophagogastric Junction, Esophageal Adenocarcinoma (UICC TNM7)
Conditions
Keywords
Esophageal neoplasms, gastro-esophageal junction neoplasms, adenocarcinoma, esophagectomy, surgery, radiotherapy, chemotherapy
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
Interventions
DRUG5-Fluorouracil
2600 mg/m² (24 hours), d1 every two weeks;
DRUGLeucovorin
200 mg/m² in 250 ml NaCl 0.9%, d1 every two weeks;
DRUGOxaliplatin
85 mg/m² in 500 ml G5% over 2h, d1 every two weeks;
DRUGDocetaxel
50mg/m2 in 250 ml NaCl 0.9% over 1h, d1 every two weeks;
DRUGCarboplatin
Dose-dependant: 2mg/ml/min AUC in 500ml Glucose 5%, day 1, 8, 15, 22 and day 29.
DRUGPaclitaxel
50mg/m2 in 500ml NaCl 0.9% over 1 h, day 1, 8, 15, 22 and day 29;
RADIATIONNeoadjuvant 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.
Sponsors
Clinical Trials Unit Freiburg
University of Freiburg
University of Leipzig
University of Luebeck
University of Hamburg-Eppendorf
University Hospital Schleswig-Holstein
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 | 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 | — |
| Postoperative complications | From time of surgery up to 90 days postoperatively | — |
| Non-surgical site complications | From time of surgery up to 90 days postoperatively | — |
Countries
Germany
Outcome results
None listed