OPPOSITE: Outcome Prediction of Systemic Treatment in Esophagogastric Carcinoma

NCT03429816 | Completed

• 1 other identifier: OPPOSITE
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

Brief Summary

Patients with locally advanced, resectable gastric or esophagogastric junction adenocarcinoma will receive a biopsy of the primary tumor, followed by standard-of care neoadjuvant systemic treatment; after neoadjuvant therapy tumor biopsies will be taken from different sites of the resection specimen.

• Aim 1: Organoid cultures of pre-treatment tumor biopsies will be established and exposed to the same chemotherapy as the corresponding patient; in vitro response to treatment will be correlated with the in vivo response of patients.
• Aim 2: Whole genome, methylome and RNA sequencing of tumors biopsies and organoids will be performed prior to as well as after systemic treatment. Histological and clinical outcome will be correlated with molecular subtypes.

Conditions

Gastric Neoplasm; Gastroesophageal Junction Adenocarcinoma; Esophageal Adenocarcinoma; Gastric Adenocarcinoma; Esophageal Neoplasms

Outcome Measures

Primary Outcomes (2)

• Aim 1: Correlation of in-vitro response in the organoid model with histological regression in the resected tumor

  Correlation of in-vitro response to cytotoxic chemotherapy in the patient-derived organoid model with histological regression in the resected specimen and analysis of reliability of this organoid model in predicting patients' response to neoadjuvant chemotherapy.

  1 year

• Aim 2: Correlation of molecular subtypes with histological response after neoadjuvant therapy in patients

  Prognostic impact of the molecular subtypes on histological response to neoadjuvant chemotherapy in patients will be modeled using the logistic regression.

  1 year

Secondary Outcomes (2)

• Aim 1: Correlation of in-vitro response in the organoid model with relapse-free survival

  maximum 5 years

• Aim 2: Correlation of molecular subtypes with relapse-free survival

  maximum 5 years

Other Outcomes (2)

• Aim 1: Correlation of in-vitro response in the organoid model with overall survival

  maximum 5 years

• Aim 2: Correlation of molecular subtypes with overall survival

  maximum 5 years

Study Arms (1)

Interventional Arm

EXPERIMENTAL

Patients with locally advanced, resectable gastric or esophagogastric junction adenocarcinoma will receive a biopsy of the primary tumor, followed by standard-of care neoadjuvant systemic treatment; after neoadjuvant therapy tumor biopsies will be taken from different sites of the resection specimen. Organoid cultures of pre-treatment tumor biopsies will be established and exposed to the same chemotherapy as the corresponding patient; in vitro response to treatment will be correlated with the in vivo response of patients. Whole genome, methylome and RNA sequencing of tumors biopsies and organoids will be performed prior to as well as after systemic treatment.

Procedure: Biopsy

Interventions

Biopsy PROCEDURE

Patients with locally advanced, resectable gastric or esophagogastric junction adenocarcinoma will receive a biopsy of the primary tumor, followed by standard-of care neoadjuvant systemic treatment; after neoadjuvant therapy tumor biopsies will be taken from different sites of the resection specimen.

Interventional Arm

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed, resectable adenocarcinoma of the GEJ (type I-III) or the stomach (cT2, cT3,cT4, any cN category, M0), or any cT cN+ M0 with the following specifications:
• ECOG-Score ≤ 2
• Patient is fit to undergo surgery (either subtotal or total gastrectomy, transhiatal or abdominothoracic esophagectomy)
• No preceding cytotoxic or targeted therapy
• No prior partial or complete tumor resection

You may not qualify if:

• Patients with distant metastasis
• Known hypersensitivity against components of the neoadjuvant systemic treatment
• Documented history of congestive heart failure NYHA ≥III, myocardial infarction within the past 3 months before the start of neoadjuvant treatment
• Uncontrollable high-risk cardiac arrhythmia, e.g. significant ventricular arrhythmia
• Past or current history of other malignancies not curatively treated and without evidence of disease for more than 5 years, except for curatively treated early stage cancers such as basal cell carcinoma of the skin and in situ carcinoma of the cervix or the bladder.

Sponsors & Collaborators

• University Hospital Heidelberg: lead
• University Hospital Dresden: collaborator
• German Cancer Research Center: collaborator

Study Sites (2)

University Hospital Dresden

Dresden, Germany

Location

National Center for Tumor Diseases, University Hospital Heidelberg

Heidelberg, Germany

Location

MeSH Terms

Conditions

Stomach Neoplasms; Adenocarcinoma Of Esophagus; Esophageal Neoplasms

Interventions

Biopsy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Georg Martin Haag

  NCT, University Hospital Heidelberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: NCT, Dep. Medical Oncology

Study Record Dates

• First Submitted: February 5, 2018
• First Posted: February 12, 2018
• Study Start: April 15, 2018
• Primary Completion: November 1, 2021
• Study Completion: November 30, 2023
• Last Updated: March 27, 2025

Record last verified: 2025-03

Locations

DE (2)