Comparison of Molecular-Genetic Concordance of the Primary Tumor and Brain Metastases of Colorectal Cancer

NCT06449989 | Recruiting

• 1 other identifier: 115522143966
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

GENCONCOR-1 study is translational research aimed to investigate the concordance of the molecular genetic profile of the primary tumor and brain metastases (BM) of colorectal cancer (CRC). The study was conducted by post hoc analysis of pairs of samples of histological material with determination of the mutational status of genes KRAS, NRAS, BRAF, HER2 and MSI.

Conditions

Colorectal Cancer Metastatic; Brain Metastases, Adult; Ras (KRAS or NRAS) Gene Mutation; BRAF Gene Mutation; HER2 Gene Mutation; MSI

Keywords

Colorectal Cancer Metastatic; Brain Metastases, Adult; Ras (KRAS or NRAS) Gene Mutation; BRAF Gene Mutation; HER2 Gene Mutation; MSI

Outcome Measures

Primary Outcomes (1)

• Concordance rate (%)

  Concordance rate (%) between mutational status of the brain lesions and their corresponding primary tumor. Calculated as the ratio of concordant cases to total cases.

  1 month

Secondary Outcomes (3)

• Intracranial progression-free survival (CNS-PFS1)

  3 months

• Overall survival (OS)

  6 months

• Intracranial progression-free survival (CNS-PFS2)

  3 months

Interventions

Tumor samples will be tested for mutation status of KRAS, NRAS, BRAF, HER2 and MSI DIAGNOSTIC_TEST

For molecular genetic research, archival formalin-fixed and paraffin-embedded tumor blocks will be used. Research method - HRM-PCR sequencing to determine mutation status of KRAS, NRAS and BRAF (RotorGene 6000, ABI Prism 3500) and fragmentation analysis to determine MSI (ABI Prism 3500) Subject to study: mutations in the KRAS, NRAS, BRAF genes, as well as MSI status and HER2neu expression (± amplification) Somatic mutations in the RAS family genes are planned to be studied in exons 2 (codons 12 and 13), exon 3 (codon 61) and exon 4 (codon 146). In the case of the BRAF gene - exon 15 (codons 597-601). Determination of microsatellite instability is planned using five markers: BAT25, BAT26, NR21, NR24, NR27, associated with structural and functional disorders of the DNA unpaired base repair system. Assessment of HER2 gene status is planned by immunohistochemical (IHC) screening of HER2neu expression. IHC-screening of HER2-status will be performed using an antibody clone 4B5 (Ventana).

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with metastatic colorectal cancer (CRC) and brain metastases (BM) will be analyzed according to sex, age, functional status (ECOG 0-1 or 2-3), number of BM (solitary or ≥ 2), clinical manifestations of BM (symptomatic or asymptomatic), extracranial lesions at the time of diagnosis BM (present or absent), course of brain metastases (synchronous with the primary tumor or metachronous), side of the location of the primary tumor (left-sided or right-sided CRC), location of intracranial lesions (supratentorial or subtentorial), number of previous lines of drug therapy.

You may qualify if:

• Men and women over 18 years of age.
• Histologically confirmed cancer of the colon or rectum.
• Histologically confirmed metastatic lesion of the brain.
• Neurosurgical resection for brain metastases of colorectal cancer.
• Presence of paired tumor samples (both primary tumor and intracranial material).

You may not qualify if:

• Missing one sample from a pair of tumor samples.
• Low quality or lack of tumor material for molecular genetic research.

Sponsors & Collaborators

• Blokhin's Russian Cancer Research Center: lead

Study Sites (1)

Blokhin's Russian Cancer Research Center

Moscow, Moscow, 115478, Russia

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Archival formalin-fixed and paraffin-embedded tumor blocks (pair of matched tumor samples: from the primary tumor and from intracranial metastases)

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Genes, mos

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Proto-Oncogenes; Oncogenes; Genes, Neoplasm; Genes; Genome Components; Genome; Genetic Structures; Genetic Phenomena

Study Officials

• Alexey Tryakin, MD, professor

  Blokhin's Russian Cancer Research Center

  STUDY CHAIR

• Ali Bekyashev, MD, professor

  Blokhin's Russian Cancer Research Center

  STUDY CHAIR

• Anna Stroganova, MD

  Blokhin's Russian Cancer Research Center

  STUDY CHAIR

Central Study Contacts

David Halafyan, MD

CONTACT

+7(930)928-00-72; daveupnow@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician-researcher

Study Record Dates

• First Submitted: June 4, 2024
• First Posted: June 10, 2024
• Study Start: April 1, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: August 12, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: From the moment of publication of the results and indefinitely
• Access Criteria: For individual participant data meta-analysis. Data will be available indefinitely in the appendix of the published article

Locations

RU (1)