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

Colorectal Cancer Metastatic Clinical Trial

— GENCONCOR-1  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06449989
• Other study ID #: 115522143966
• Status: Recruiting
• Start date: April 1, 2024
• Est. completion date: April 2025

Study information

• Verified date: June 2024
• Source: Blokhin's Russian Cancer Research Center
• Contact: David Halafyan, MD
• Phone: +7(930)928-00-72
• Email: daveupnow[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

Brain metastases (BM) from colorectal cancer (CRC) are a rare event reported in less than 3% of patients with CRC (the reported incidence ranges from 0.27 to 3%). This course is associated with a poor prognosis. Treatment of these patients remains challenging. Nevertheless, given the rarity of the event, at this time not enough is known about molecular biology of BM from colorectal cancer and its concordance with matched primary tumors. In N.N. Blokhin National Medical Research Center of Oncology over 26 years (1998-2024) identified 108 patients with BM from CRC. Of this number, 72 patients had a history of neurosurgical resection of BM. In turn, for 32 patients access to a pair of tumor samples: from the primary tumor and from intracranial metastases. Tumor samples will be tested for mutation status of genes KRAS, NRAS, BRAF, HER2 and MSI. Analysis was limited to this pool of genes because of their clinical relevance and potential prognostic information. The molecular profile of the BM will be compared with the corresponding primary tumor with calculation of concordance rate (%).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Men and women over 18 years of age.

2. Histologically confirmed cancer of the colon or rectum.

3. Histologically confirmed metastatic lesion of the brain.

4. Neurosurgical resection for brain metastases of colorectal cancer.

5. Presence of paired tumor samples (both primary tumor and intracranial material).

Exclusion Criteria:

1. Missing one sample from a pair of tumor samples.

2. Low quality or lack of tumor material for molecular genetic research.

Related Conditions & MeSH terms

• BRAF Gene Mutation
• Brain Metastases, Adult
• Brain Neoplasms
• Colorectal Cancer Metastatic
• Colorectal Neoplasms
• HER2 Gene Mutation
• MSI
• Neoplasm Metastasis

Intervention

Diagnostic Test:
• Tumor samples will be tested for mutation status of KRAS, NRAS, BRAF, HER2 and MSI
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).

Locations

Country	Name	City	State
Russian Federation	Blokhin's Russian Cancer Research Center	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
Blokhin's Russian Cancer Research Center

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Intracranial progression-free survival (CNS-PFS1)	Time from the date of cancer diagnosis to the date of detection of brain metastases.	3 months
Secondary	Overall survival (OS)	Time from the date of detection of brain metastases to the date of death.	6 months
Secondary	Intracranial progression-free survival (CNS-PFS2)	Time from the date of neurosurgical resection to the date of intracranial progression (continued growth or distant brain metastases) or death.	3 months