Clinical trial NCT06449989: Comparison of Molecular-Genetic Concordance of the Primary Tumor and Brain Metastases of Colorectal Cancer
Official title: Comparison of Molecular-Genetic Concordance of the Primary Tumor and Brain Metastases of Colorectal Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: Blokhin's Russian Cancer Research Center
Sponsor class: OTHER
First posted: 2024-06-10
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

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.

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 (%).

Eligibility criteria: 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.

Primary outcomes:
measure: Concordance rate (%)
timeFrame: 1 month
Secondary outcomes:
measure: Intracranial progression-free survival (CNS-PFS1)
timeFrame: 3 months
measure: Overall survival (OS)
timeFrame: 6 months
measure: Intracranial progression-free survival (CNS-PFS2)
timeFrame: 3 months
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Blokhin's Russian Cancer Research Center
Study officials:
affiliation: Blokhin's Russian Cancer Research Center
name: Alexey Tryakin, MD, professor
role: STUDY_CHAIR
affiliation: Blokhin's Russian Cancer Research Center
name: Ali Bekyashev, MD, professor
role: STUDY_CHAIR
affiliation: Blokhin's Russian Cancer Research Center
name: Anna Stroganova, MD
role: STUDY_CHAIR
References: