Esophageal Cancer
Conditions
Keywords
esophageal-gastric junction cancer, preoperative chemoradiotherapy, BIRC3
Brief summary
Preoperative chemoradiotherapy followed by surgery has been accepted as the standard of care for resectable adenocarcinoma of the esophagus and esophagogastric junction (EGJ). However, in a large part of the cases the tumor is extremely resistant to chemoradiotherapy, and those patients do not benefit from this treatment but are exposed to its negative consequences such as toxicity and delayed surgical therapy. The hypothesis is that a biomarker-driven therapeutic strategy in which patients will receive preoperative chemoradiotherapy or upfront surgery based on the basal tumor expression of BIRC3 could improve the R0 resection rate if compared with a standard strategy in unselected patients.
Detailed description
BoRgES trial is a multicenter, randomized phase II study of BIRC3-expression directed preoperative chemoradiotherapy in patients with resectable adenocarcinoma of the esophagus and EGJ. The main objective of this proposal is to provide evidence for a novel therapeutic strategy with enormous significance for patients affected by this disease. Only a part of the patients with esophageal adenocarcinoma benefit from neoadjuvant therapy, and the clinical efficacy of chemoradiotherapy is reduced by the pre-existence of cellular drug resistance. Thus, there is an urgent need to identify patients who could not benefit from preoperative treatment. The study will define an innovative therapeutic strategy directed by the expression of BIRC3 as a predictive marker for discriminating patients who will most likely be resistant to preoperative chemoradiotherapy.
Interventions
OTHERBIRC3
BIRC3-expression directed preoperative chemoradiotherapy in patients with resectable adenocarcinoma of the esophagus and EGJ
Sponsors
Azienda Ospedaliera Universitaria Integrata Verona
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
open-label, multicenter, randomized phase II study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven adenocarcinoma of the esophagus and EGJ (Siewert I/II) surgical resectable (cT2-4a, N0-1, M0), as determined by Endoscopic Ultra Sound (EUS) and or PET-TC scan. cT1N1 tumors are eligible, T1N0 tumors and in situ carcinoma are not eligible. * If tumor extends below the EGJ junction into the proximal stomach, the bulk of the tumor must involve the esophagus or GE junction. The tumor must not extend more than 2 cm into the stomach (Siewert III). Gastric cancers with minor involvement of the GE junction or esophagus are not eligible. * Age \>18, no age upper limit unless patient would be unable to tolerate chemoradiotherapy. * Have given written informed consent prior to any study-specific procedures. * ECOG performance status 0-2. * No prior thoracic radiotherapy allowed. * Adequate hematological, renal, cardiac, hepatic and pulmonary functions.
Exclusion criteria
\-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| R0, number of patients achieving R0 resection. | 3 years | number of patients achieving R0 resection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OS | 3 years | overall survival |
| DFS | 3 years | disease free survival |
| tumour response | 3 years | tumour response evaluated either by Mandard's tumour regression grade |
| safety profile | 3 years | safety profile (incidence of ≥ grade 3 adverse events using Common Terminology Criteria for Adverse Events - CTCAE - version 4.0). |
Outcome results
None listed