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

NCT04269083 | Unknown DMC

• 1 other identifier: GR-2016-02361134
• Study Type: interventional
• Target: 128
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Esophageal Cancer

Keywords

esophageal-gastric junction cancer, preoperative chemoradiotherapy, BIRC3

Outcome Measures

Primary Outcomes (1)

• R0, number of patients achieving R0 resection.

  number of patients achieving R0 resection.

  3 years

Secondary Outcomes (4)

• OS

  3 years

• DFS

  3 years

• tumour response

  3 years

• safety profile

  3 years

Study Arms (2)

experimental arm

EXPERIMENTAL

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.

Other: BIRC3

control arm

ACTIVE COMPARATOR

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.

Other: BIRC3

Interventions

BIRC3 OTHER

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

control arm; experimental arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• Azienda Ospedaliera Universitaria Integrata Verona: lead

MeSH Terms

Conditions

Esophageal Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: open-label, multicenter, randomized phase II study

Study Record Dates

• First Submitted: February 6, 2020
• First Posted: February 13, 2020
• Study Start: May 24, 2020
• Primary Completion: March 24, 2024
• Study Completion: August 24, 2024
• Last Updated: April 17, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share