OPPOSITE: Outcome Prediction Of Systemic Treatment in Esophagogastric Carcinoma
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Aim 1: Correlation of in-vitro response in the organoid model with histological regression in the resected tumor [1 year]
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 [1 year]
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 [maximum 5 years]
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 [maximum 5 years]
The possible prognostic impact of molecular subtypes on relapse-free survival will be investigated using the Cox proportional hazards models.
Other Outcome Measures
- Aim 1: Correlation of in-vitro response in the organoid model with overall survival [maximum 5 years]
The possible prognostic impact of in-vitro response in the organoid model on overall survival will be investigated using the Cox proportional hazards models.
- Aim 2: Correlation of molecular subtypes with overall survival [maximum 5 years]
The possible prognostic impact of molecular subtypes on overall survival will be investigated using the Cox proportional hazards models.
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital Dresden | Dresden | Germany | ||
| 2 | National Center for Tumor Diseases, University Hospital Heidelberg | Heidelberg | Germany |
Sponsors and Collaborators
- University Hospital Heidelberg
- University Hospital Dresden
- German Cancer Research Center
Investigators
- Principal Investigator: Georg Martin Haag, NCT, University Hospital Heidelberg
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- OPPOSITE