Back to resultsOPPOSITE: Outcome Prediction Of Systemic Treatment in Esophagogastric Carcinoma (OPPOSITE)
Primary Purpose
Gastric Neoplasm, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma
Status
Active
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Biopsy
Sponsored by
About this trial
This is an interventional diagnostic trial for Gastric Neoplasm
Eligibility Criteria
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.
Sites / Locations
- University Hospital Dresden
- National Center for Tumor Diseases, University Hospital Heidelberg
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Interventional Arm
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT03429816
First Posted
February 5, 2018
Last Updated
May 8, 2023
Sponsor
University Hospital Heidelberg
Collaborators
University Hospital Dresden, German Cancer Research Center
1. Study Identification
Unique Protocol Identification Number
NCT03429816
Brief Title
OPPOSITE: Outcome Prediction Of Systemic Treatment in Esophagogastric Carcinoma
Acronym
OPPOSITE
Official Title
Molecular Outcome Prediction of Neoadjuvant Systemic Treatment in Esophagogastric Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 15, 2018 (Actual)
Primary Completion Date
November 1, 2021 (Actual)
Study Completion Date
November 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital Heidelberg
Collaborators
University Hospital Dresden, German Cancer Research Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Neoplasm, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma, Gastric Adenocarcinoma, Esophageal Neoplasms
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Interventional Arm
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Biopsy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Aim 1: Correlation of in-vitro response in the organoid model with histological regression in the resected tumor
Description
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.
Time Frame
1 year
Title
Aim 2: Correlation of molecular subtypes with histological response after neoadjuvant therapy in patients
Description
Prognostic impact of the molecular subtypes on histological response to neoadjuvant chemotherapy in patients will be modeled using the logistic regression.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Aim 1: Correlation of in-vitro response in the organoid model with relapse-free survival
Description
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.
Time Frame
maximum 5 years
Title
Aim 2: Correlation of molecular subtypes with relapse-free survival
Description
The possible prognostic impact of molecular subtypes on relapse-free survival will be investigated using the Cox proportional hazards models.
Time Frame
maximum 5 years
Other Pre-specified Outcome Measures:
Title
Aim 1: Correlation of in-vitro response in the organoid model with overall survival
Description
The possible prognostic impact of in-vitro response in the organoid model on overall survival will be investigated using the Cox proportional hazards models.
Time Frame
maximum 5 years
Title
Aim 2: Correlation of molecular subtypes with overall survival
Description
The possible prognostic impact of molecular subtypes on overall survival will be investigated using the Cox proportional hazards models.
Time Frame
maximum 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Georg Martin Haag
Organizational Affiliation
NCT, University Hospital Heidelberg
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Dresden
City
Dresden
Country
Germany
Facility Name
National Center for Tumor Diseases, University Hospital Heidelberg
City
Heidelberg
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
OPPOSITE: Outcome Prediction Of Systemic Treatment in Esophagogastric Carcinoma
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