Comparison of Molecular-Genetic Concordance of the Primary Tumor and Brain Metastases of Colorectal Cancer (GENCONCOR-1)

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer Metastatic; Brain Metastases, Adult; HER2 Gene Mutation; MSI; BRAF Gene Mutation; Ras (KRAS or NRAS) Gene Mutation
• Intervention / Treatment: Diagnostic test: Tumor samples will be tested for mutation status of KRAS, NRAS, BRAF, HER2 and MSI

Detailed 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 (%).

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: David Halafyan, MD; Phone Number: +7(930)928-00-72; Email: daveupnow@gmail.com

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115478
    • Recruiting
    • Blokhin's Russian Cancer Research Center
    • Contact: David Halafyan, MD; Phone Number: +7(930)928-00-72; Email: daveupnow@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial progression-free survival (CNS-PFS1)	Time from the date of cancer diagnosis to the date of detection of brain metastases.	3 months
Overall survival (OS)	Time from the date of detection of brain metastases to the date of death.	6 months
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

Collaborators and Investigators

• Sponsor: Blokhin's Russian Cancer Research Center
• Investigators: Study Chair: 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 record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: June 4, 2024
• First Submitted That Met QC Criteria: June 4, 2024
• First Posted (Actual): June 10, 2024

Study Record Updates

• Last Update Posted (Actual): August 12, 2025
• Last Update Submitted That Met QC Criteria: August 7, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Colorectal Cancer Metastatic; BRAF Gene Mutation; MSI; HER2 Gene Mutation; Brain Metastases, Adult; Ras (KRAS or NRAS) Gene Mutation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Neoplastic Processes; Nervous System Neoplasms; Central Nervous System Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: 115522143966

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underline the results reported in article, after deidentification (text, tables, figures, and appendices)
• IPD Sharing Time Frame: From the moment of publication of the results and indefinitely
• IPD Sharing Access Criteria: For individual participant data meta-analysis. Data will be available indefinitely in the appendix of the published article

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No