OPPOSITE: Outcome Prediction Of Systemic Treatment in Esophagogastric Carcinoma (OPPOSITE)

Molecular Outcome Prediction of Neoadjuvant Systemic Treatment in Esophagogastric Carcinoma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Esophageal Neoplasms; Gastric Adenocarcinoma; Esophageal Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Gastric Neoplasm
• Intervention / Treatment: Procedure: Biopsy

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Dresden, Germany
    • University Hospital Dresden
  • Heidelberg, Germany
    • National Center for Tumor Diseases, University Hospital Heidelberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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
• Exclusion of distant metastasis by CT or MRI of thorax and abdomen, and optionally bone scan (if osseous lesions are suspected due to clinical signs)

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Interventional Arm; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aim 1: Correlation of in-vitro response in the organoid model with relapse-free survival	The possible prognostic impact of in-vitro response in the organoid model on relapse-free survival will be investigated using the Cox proportional hazards models.	maximum 5 years
Aim 2: Correlation of molecular subtypes with relapse-free survival	The possible prognostic impact of molecular subtypes on relapse-free survival will be investigated using the Cox proportional hazards models.	maximum 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aim 1: Correlation of in-vitro response in the organoid model with overall survival	The possible prognostic impact of in-vitro response in the organoid model on overall survival will be investigated using the Cox proportional hazards models.	maximum 5 years
Aim 2: Correlation of molecular subtypes with overall survival	The possible prognostic impact of molecular subtypes on overall survival will be investigated using the Cox proportional hazards models.	maximum 5 years

Collaborators and Investigators

• Sponsor: University Hospital Heidelberg
• Collaborators: German Cancer Research Center; University Hospital Dresden
• Investigators: Principal Investigator: Georg Martin Haag, NCT, University Hospital Heidelberg

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2018
• Primary Completion (Actual): November 1, 2021
• Study Completion (Anticipated): November 1, 2023

Study Registration Dates

• First Submitted: February 5, 2018
• First Submitted That Met QC Criteria: February 5, 2018
• First Posted (Actual): February 12, 2018

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms; Stomach Neoplasms; Adenocarcinoma; Esophageal Neoplasms
• Other Study ID Numbers: OPPOSITE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No