Clinical trial · Interventional
Perioperative Chemotherapy Compared To Neoadjuvant Chemoradiation in Patients With Adenocarcinoma of the Esophagus
Perioperative Chemotherapy (FLOT Protocol) Compared To Neoadjuvant Chemoradiation (CROSS Protocol) in Patients With Adenocarcinoma of the Esophagus
NCT02509286CI-TRIAL-00076907ESOPECunknownPhase 3ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Adenocarcinoma of the Esophagogastric Junction | Gastroesophageal Junction Adenocarcinoma | ALIAS | 0.90 |
| Esophageal Adenocarcinoma (UICC TNM7) | Esophageal Adenocarcinoma | ONTOLOGY_EXACT | 0.85 |
Interventions
Interventions (7)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| 5-Fluorouracil | Drug | Fluorouracil | ALIAS |
| Carboplatin | Drug | Carboplatin | ALIAS |
| Docetaxel | Drug | Docetaxel | ALIAS |
| Leucovorin | Drug | Leucovorin | ALIAS |
| Neoadjuvant radiation | Radiation | — | UNRESOLVED |
| Oxaliplatin | Drug | Oxaliplatin | ALIAS |
| Paclitaxel | Drug | Paclitaxel | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Perioperative Chemotherapy (FLOT):
- 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.
- interventionNames
- Drug: 5-Fluorouracil
- Drug: Leucovorin
- Drug: Oxaliplatin
- Drug: Docetaxel
- type
- ACTIVE_COMPARATOR
- label
- Neoadjuvant Chemoradiation (CROSS):
- 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.
- interventionNames
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (2)
- BACKGROUNDHoeppner 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
- DERIVEDHoeppner 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