Comparison of Molecular-Genetic Concordance of the Primary Tumor and Brain Metastases of Gastroesophageal Cancers
GENCONCOR-2
1 other identifier
observational
30
1 country
1
Brief Summary
GENCONCOR-2 is a translational research aimed to compare the molecular profile of primary tumors and their matched brain metastases in gastroesophageal cancers, including cancer of the esophagus, gastroesophageal junction, and stomach. The study is based on the previously established international GASTROBRAIN cohort (ClinicalTrials.gov ID: NCT07448493), which provides comprehensive clinicopathological and treatment data for over 230 patients. It will be conducted by retrospective analysis of paired samples of histological material (primary tumor and corresponding brain metastasis) with determination of HER2 expression status (IHC ± FISH), MSI status (IHC ± PCR), PD-L1 combined positive score (CPS), and CLDN18.2 expression status (IHC)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for all trials
Started Apr 2026
Typical duration for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 6, 2026
CompletedFirst Posted
Study publicly available on registry
March 11, 2026
CompletedStudy Start
First participant enrolled
April 1, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2028
March 12, 2026
March 1, 2026
2.5 years
March 6, 2026
March 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Molecular Discordance Rate (%)
Proportion of cases with discordant biomarker status (HER2, MSI, PD-L1 CPS, CLDN18.2) between primary gastroesophageal cancer and matched brain metastasis, calculated as the number of discordant pairs divided by total number of analyzed paired samples. Discordance will be assessed both overall and for each individual biomarker.
At time of molecular analysis (samples collected retrospectively; analysis will be completed within 12 months of study initiation)
Secondary Outcomes (3)
Overall Survival (OS)
From date of brain metastasis diagnosis until death or last contact, assessed up to 5 years (retrospective analysis; data will be collected from existing medical records)
Time to Intracranial Progression (TTIP)
From date of initial cancer diagnosis until first brain metastasis detection, assessed up to 10 years (retrospective analysis; data will be collected from existing medical records)
Central Nervous System Progression-Free Survival (CNS-PFS)
From the date of first local treatment for BM until subsequent intracranial progression or last imaging follow-up, assessed up to 5 years (retrospective analysis; data will be collected from existing medical records)
Study Arms (3)
Gastric Cancer Cohort
Patients with histologically confirmed gastric adenocarcinoma and paired tissue samples of primary tumor and corresponding brain metastasis.
Esophageal Cancer Cohort
Patients with histologically confirmed esophageal carcinoma (adenocarcinoma or squamous cell carcinoma) and paired tissue samples of primary tumor and corresponding brain metastasis.
Gastroesophageal Junction Cancer Cohort
Patients with histologically confirmed adenocarcinoma of the gastroesophageal junction (Siewert types I-III) and paired tissue samples of primary tumor and corresponding brain metastasis.
Interventions
Assessment of HER2 status by immunohistochemistry (IHC) using SP3 antibody clone (DAKO) on Ventana GX platform with OptiView detection system. Cases with IHC 2+ will undergo confirmatory in situ hybridization (FISH, CISH, or SISH).
Determination of microsatellite instability status by immunohistochemistry (IHC) for mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) ± PCR-based analysis using five mononucleotide repeat markers (BAT25, BAT26, NR21, NR24, NR27).
Assessment of PD-L1 expression by immunohistochemistry (IHC) using DAKO 22C3 antibody clone on Dako Link48 platform with EnVision Flex detection system. Results reported as Combined Positive Score (CPS), defined as number of PD-L1-stained cells divided by total viable tumor cells, multiplied by 100.
Assessment of CLDN18.2 expression by immunohistochemistry (IHC) using VENTANA CLDN18 (43-14A) assay on Ventana platform. Positive expression defined as moderate-to-strong (2+/3+) complete, basolateral, or lateral membranous staining in ≥ 75% of viable tumor cells.
Eligibility Criteria
The study population consists of adult patients (≥ 18 years) with histologically confirmed adenocarcinoma of the stomach, adenocarcinoma or squamous cell carcinoma of the esophagus, or adenocarcinoma of the gastroesophageal junction, and radiologically ± histologically documented brain metastases. All patients were previously enrolled in the parent GASTROBRAIN study and have available paired archival FFPE tissue samples from both the primary tumor and the matched brain metastasis.
You may qualify if:
- Men and women aged 18 years or older included in the GASTROBRAIN study with available clinicopathological and treatment data.
- Histologically confirmed gastric adenocarcinoma, esophageal carcinoma (adenocarcinoma or squamous cell carcinoma), or gastroesophageal junction adenocarcinoma.
- History of neurosurgical resection of brain metastases with available archival tissue material, and histological confirmation of metastatic lesion originating from gastroesophageal cancer.
- Availability of paired FFPE tissue samples from primary tumor and matched brain metastasis.
You may not qualify if:
- Synchronous or metachronous multiple primary malignancies involving sites other than the stomach, esophagus, or gastroesophageal junction.
- Primary tumor located outside the gastrointestinal tract.
- Histologically confirmed non-epithelial gastrointestinal malignancy (e.g., neuroendocrine tumors, sarcoma, gastrointestinal stromal tumor, lymphoma).
- Intact brain parenchyma (e.g., metastases confined to skull bones or soft tissues of the head without brain parenchymal involvement).
- Insufficient tumor material or poor sample quality for molecular analysis, defined as:
- Tumor cell content \< 70% in the area of microdissection, or
- Significant nucleic acid degradation compromising molecular testing
- Missing one sample from a paired set (either primary tumor or brain metastasis unavailable).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Blokhin's Russian Cancer Research Center
Moscow, 115478, Russia
Related Links
Biospecimen
Archival formalin-fixed paraffin-embedded (FFPE) tissue samples - paired primary tumor and corresponding brain metastasis samples
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Alexey Tryakin, MD, PhD, professor
Blokhin's Russian Cancer Research Center
- STUDY CHAIR
Ali Bekyashev, MD, PhD, professor
Blokhin's Russian Cancer Research Center
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- RETROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- MD
Study Record Dates
First Submitted
March 6, 2026
First Posted
March 11, 2026
Study Start
April 1, 2026
Primary Completion (Estimated)
October 1, 2028
Study Completion (Estimated)
October 1, 2028
Last Updated
March 12, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- Individual participant data and supporting information will become available 6 months after publication of the primary results and will remain available for 5 years following article publication.
- Access Criteria
- Data will be shared with qualified academic researchers who submit a methodologically sound research proposal for use approved by an independent review committee. Proposals should be directed to the corresponding author. Data will be shared via a secure file transfer protocol after a data use agreement is signed.
De-identified individual participant data collected for this study will be available upon reasonable request. The data will include molecular biomarker results (HER2, MSI, PD-L1 CPS, CLDN18.2) for paired primary tumor and brain metastasis samples, as well as associated clinicopathological and treatment data from the parent GASTROBRAIN study.