A Biomarker-driven Therapeutic Strategy for Esophageal Cancer Chemoradiotherapy in Patients With Resectable Adenocarcinoma of the ESophagus and Esophagogastric Junction

Overview

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.

Full Title of Study: “A Biomarker-driven Therapeutic Strategy for Esophageal Cancer, the BoRgES Trial: a Multicenter Randomized Phase II Study of BIRC3-expression Directed Preoperative Chemoradiotherapy in Patients With Resectable Adenocarcinoma of the ESophagus and Esophagogastric Junction”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: March 24, 2024

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

  • Other: BIRC3
    • BIRC3-expression directed preoperative chemoradiotherapy in patients with resectable adenocarcinoma of the esophagus and EGJ

Arms, Groups and Cohorts

  • Experimental: experimental arm
    • fresh specimens from the tumour and normal mucosa will be collected endoscopically at diagnosis and placed immediately into RNALater to isolate RNA. The mRNA expression of BIRC3 will be quantified using a SYBR green-based real-time PCR analysis; the BIRC3 median expression in normal mucosa samples will be used as calibrator. Patients with a tumor expression level of BIRC3 lower than the established cutoff will receive a standard carboplatin/paclitaxel regimen with concurrent radiotherapy followed by surgery. Patients with an expression of BIRC3 higher or equal than the cutoff (chemoradiation resistant patients) will undergo upfront surgery.
  • Active Comparator: control arm
    • fresh specimens from the tumour and normal mucosa will be collected endoscopically at diagnosis and placed immediately into RNALater to isolate RNA. The mRNA expression of BIRC3 will be quantified using a SYBR green-based real-time PCR analysis; the BIRC3 median expression in normal mucosa samples will be used as calibrator. Patients with a tumor expression level of BIRC3 lower than the established cutoff will receive a standard carboplatin/paclitaxel regimen with concurrent radiotherapy followed by surgery. Patients with an expression of BIRC3 higher or equal than the cutoff (chemoradiation resistant patients) will undergo upfront surgery.

Clinical Trial Outcome Measures

Primary Measures

  • R0, number of patients achieving R0 resection.
    • Time Frame: 3 years
    • number of patients achieving R0 resection.

Secondary Measures

  • OS
    • Time Frame: 3 years
    • overall survival
  • DFS
    • Time Frame: 3 years
    • disease free survival
  • tumour response
    • Time Frame: 3 years
    • tumour response evaluated either by Mandard’s tumour regression grade
  • safety profile
    • Time Frame: 3 years
    • safety profile (incidence of ≥ grade 3 adverse events using Common Terminology Criteria for Adverse Events – CTCAE – version 4.0).

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Azienda Ospedaliera Universitaria Integrata Verona
  • Provider of Information About this Clinical Study
    • Sponsor

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.