search
Back to results

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

Primary Purpose

Esophageal Cancer

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
BIRC3
Sponsored by
Azienda Ospedaliera Universitaria Integrata Verona
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Cancer focused on measuring esophageal-gastric junction cancer, preoperative chemoradiotherapy, BIRC3

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

-

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    experimental arm

    control arm

    Arm Description

    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.

    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.

    Outcomes

    Primary Outcome Measures

    R0, number of patients achieving R0 resection.
    number of patients achieving R0 resection.

    Secondary Outcome Measures

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

    Full Information

    First Posted
    February 6, 2020
    Last Updated
    April 16, 2020
    Sponsor
    Azienda Ospedaliera Universitaria Integrata Verona
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT04269083
    Brief Title
    A Biomarker-driven Therapeutic Strategy for Esophageal Cancer Chemoradiotherapy in Patients With Resectable Adenocarcinoma of the ESophagus and Esophagogastric Junction
    Acronym
    BoRgES
    Official Title
    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
    Interventional

    2. Study Status

    Record Verification Date
    February 2020
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    May 24, 2020 (Anticipated)
    Primary Completion Date
    March 24, 2024 (Anticipated)
    Study Completion Date
    August 24, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Azienda Ospedaliera Universitaria Integrata Verona

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Esophageal Cancer
    Keywords
    esophageal-gastric junction cancer, preoperative chemoradiotherapy, BIRC3

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    open-label, multicenter, randomized phase II study
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    128 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    experimental arm
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    control arm
    Arm Type
    Active Comparator
    Arm Description
    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.
    Intervention Type
    Other
    Intervention Name(s)
    BIRC3
    Intervention Description
    BIRC3-expression directed preoperative chemoradiotherapy in patients with resectable adenocarcinoma of the esophagus and EGJ
    Primary Outcome Measure Information:
    Title
    R0, number of patients achieving R0 resection.
    Description
    number of patients achieving R0 resection.
    Time Frame
    3 years
    Secondary Outcome Measure Information:
    Title
    OS
    Description
    overall survival
    Time Frame
    3 years
    Title
    DFS
    Description
    disease free survival
    Time Frame
    3 years
    Title
    tumour response
    Description
    tumour response evaluated either by Mandard's tumour regression grade
    Time Frame
    3 years
    Title
    safety profile
    Description
    safety profile (incidence of ≥ grade 3 adverse events using Common Terminology Criteria for Adverse Events - CTCAE - version 4.0).
    Time Frame
    3 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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: -

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

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

    We'll reach out to this number within 24 hrs