OPPOSITE: Outcome Prediction Of Systemic Treatment in Esophagogastric Carcinoma

Gastric Adenocarcinoma Clinical Trial

— OPPOSITE  

Official title:

Molecular Outcome Prediction of Neoadjuvant Systemic Treatment in Esophagogastric Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03429816
• Other study ID #: OPPOSITE
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 15, 2018
• Est. completion date: November 2023

Study information

• Verified date: May 2023
• Source: University Hospital Heidelberg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: November 2023
• Est. primary completion date: November 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Esophageal Adenocarcinoma
• Esophageal Neoplasms
• Gastric Adenocarcinoma
• Gastric Neoplasm
• Gastroesophageal Junction Adenocarcinoma
• Neoplasms
• Stomach Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Germany	University Hospital Dresden	Dresden
Germany	National Center for Tumor Diseases, University Hospital Heidelberg	Heidelberg

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital Heidelberg	German Cancer Research Center, University Hospital Dresden

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	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
Primary	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	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
Secondary	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