NCT02509286 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: UNKNOWN
Registry last update: 2024-05-08

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.

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part

eligibility Criteria: 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

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.
intervention Names
Drug: 5-Fluorouracil
Drug: Leucovorin
Drug: Oxaliplatin
Drug: Docetaxel
label
Perioperative Chemotherapy (FLOT):
type
EXPERIMENTAL
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.
intervention Names
Drug: Carboplatin
Drug: Paclitaxel
Radiation: Neoadjuvant radiation
label
Neoadjuvant Chemoradiation (CROSS):
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Perioperative Chemotherapy (FLOT):
description
2600 mg/m² (24 hours), d1 every two weeks;
name
5-Fluorouracil
type
DRUG
arm Group Labels
Perioperative Chemotherapy (FLOT):
description
200 mg/m² in 250 ml NaCl 0.9%, d1 every two weeks;
name
Leucovorin
type
DRUG
arm Group Labels
Perioperative Chemotherapy (FLOT):
description
85 mg/m² in 500 ml G5% over 2h, d1 every two weeks;
name
Oxaliplatin
type
DRUG
arm Group Labels
Perioperative Chemotherapy (FLOT):
description
50mg/m2 in 250 ml NaCl 0.9% over 1h, d1 every two weeks;
name
Docetaxel
type
DRUG
arm Group Labels
Neoadjuvant Chemoradiation (CROSS):
description
Dose-dependant: 2mg/ml/min AUC in 500ml Glucose 5%, day 1, 8, 15, 22 and day 29.
name
Carboplatin
type
DRUG
arm Group Labels
Neoadjuvant Chemoradiation (CROSS):
description
50mg/m2 in 500ml NaCl 0.9% over 1 h, day 1, 8, 15, 22 and day 29;
name
Paclitaxel
type
DRUG
arm Group Labels
Neoadjuvant Chemoradiation (CROSS):
description
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.
name
Neoadjuvant radiation
type
RADIATION

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 438
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Overall survival will be calculated as time from start of study treatment to death due to any cause.
measure
Overall survival
time Frame
At end of trial- up to 3 years in follow up

secondary Outcomes

description
PFS will be calculated as the time interval from randomisation to the first event of locoregional failure, metastatic progression or death.
measure
Progression free survival time (PFS)
time Frame
From randomisation up to 3 years in follow up
measure
Site of failure: local, regional or distant Failure
time Frame
From time of surgery up to 3 years in follow up
description
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.
measure
Recurrence free survival time
time Frame
From time of surgery up to 3 years in follow up
measure
Postsurgical Quality of Life
time Frame
From randomization up to 3 years in follow up
measure
Postoperative complications
time Frame
From time of surgery up to 90 days postoperatively
measure
Non-surgical site complications
time Frame
From time of surgery up to 90 days postoperatively

Full study description

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

Source references

references

citation
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
type
BACKGROUND
citation
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
type
DERIVED