Clinical trial NCT03429816: OPPOSITE: Outcome Prediction of Systemic Treatment in Esophagogastric Carcinoma
Official title: Molecular Outcome Prediction of Neoadjuvant Systemic Treatment in Esophagogastric Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gastric Neoplasm
Gastroesophageal Junction Adenocarcinoma
Esophageal Adenocarcinoma
Gastric Adenocarcinoma
Esophageal Neoplasms
Lead sponsor: University Hospital Heidelberg
Sponsor class: OTHER
Collaborators: name: University Hospital Dresden
name: German Cancer Research Center
First posted: 2018-02-12
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.


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.

Primary outcomes:
measure: Aim 1: Correlation of in-vitro response in the organoid model with histological regression in the resected tumor
timeFrame: 1 year
measure: Aim 2: Correlation of molecular subtypes with histological response after neoadjuvant therapy in patients
timeFrame: 1 year
Secondary outcomes:
measure: Aim 1: Correlation of in-vitro response in the organoid model with relapse-free survival
timeFrame: maximum 5 years
measure: Aim 2: Correlation of molecular subtypes with relapse-free survival
timeFrame: maximum 5 years
Other outcomes:
measure: Aim 1: Correlation of in-vitro response in the organoid model with overall survival
timeFrame: maximum 5 years
measure: Aim 2: Correlation of molecular subtypes with overall survival
timeFrame: maximum 5 years
Locations:
city: Dresden
country: Germany
facility: University Hospital Dresden
city: Heidelberg
country: Germany
facility: National Center for Tumor Diseases, University Hospital Heidelberg
Study officials:
affiliation: NCT, University Hospital Heidelberg
name: Georg Martin Haag
role: PRINCIPAL_INVESTIGATOR
References: