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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06414304
Other study ID # BLOOMSI
Secondary ID 22-75-10154
Status Recruiting
Phase
First received
Last updated
Start date June 1, 2022
Est. completion date July 2026

Study information

Verified date May 2024
Source OncoAtlas LLC
Contact Maxim Ivanov, PhD
Phone +7 909 677-52-74
Email maxim.ivanov@oncoatlas.ru
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Microsatellite instability or mismatch repair deficiency occurs in 20% of CRC, and is predominantly found in non-metastatic tumors. The success of the CheckMate 142 and KEYNOTE-177 clinical trials has shifted the treatment paradigm of the MSI/dMMR CRC, which has led to the adoption of immune checkpoint inhibitors (ICI) by international treatment standards. However, despite the encouraging effects of ICI, up to 30% of patients are resistant to treatment and exhibit rapid disease progression shortly after starting ICI. On the other hand, around 30% of patients treated with ICI demonstrate prolonged responses to the treatment with a duration of response of over 40 months. Furthermore, for ~10% of patients, treatment with ICI results in pseudo-progression - a phenomenon of a short-term increase followed by the decrease of the tumor volume. Currently, the mechanisms and biomarkers associated with the response or resistance to ICI in MSI-positive CRC are largely unknown. Select studies suggest that BRAF mutations (specifically, BRAF p.V600E) might negatively affect the patients' progression-free survival following ICI, however, these data are premature. The primary hypothesis is that the clonal heterogeneity and the evolution of MSI status of MSI-positive CRC will play a role in the development of ICI treatment resistance. The primary objective of the study is to investigate the dynamics of MSI status in serial liquid biopsy samples from patients with MSI-positive tumors receiving ICI.


Description:

This is a multicenter observational trial designed to evaluate the dynamics of microsatellite instability and the genomic profiles of CRC during immune checkpoint inhibitor treatment. Patients with MSI/dMMR-positive tumors who are candidates for the ICI treatment will be included in the study. MSI/dMMR positivity should be confirmed with polymerase chain reaction-based (PCR) assays, immunohistochemistry (IHC) or Next-generation sequencing (NGS). Treatment with any ICI will be allowed. Upon inclusion in the study, patients will be asked to provide the pre-treatment FFPE tumor and liquid biopsy (LB) samples along with LB samples on the 14th, 28th days of ICI, and at every control study. LB samples will be collected until treatment discontinuation. The pre-treatment FFPE samples will be tested with an alternative routine method (PCR and/or IHC, depending on what method was used for initial testing), as well as with the Solo Atlas Pro NGS panel covering common cancer-related genes and short tandem repeats for MSI detection. All LB samples will be tested with the Solo Atlas Pro NGS panel. Dynamics of MSI and genomic profiles will be correlated with the treatment outcomes. Disease response to study treatment will be evaluated by imaging methods. Response to treatment will be determined by RECIST v1.1.


Recruitment information / eligibility

Status Recruiting
Enrollment 70
Est. completion date July 2026
Est. primary completion date July 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Male/female participants must be at least 18 years of age on the day of signing informed consent and have a histologically confirmed diagnosis of colorectal cancer. - Verified MSI/dMMR positivity as measured by 5-loci PCR or 4-antibody IHC. - The patient is scheduled to start treatment with any of the immune checkpoint inhibitors 2-4 weeks after the inclusion in the study. - Have provided an archival tumor tissue sample obtained prior to the start of treatment with immune checkpoint inhibitor(s). Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. - Patient has to be able to provide serial blood samples during the course of treatment, as well as on every follow-up tumor scan. - The participant (or legally acceptable representative if applicable) provides written informed consent to participate in the trial. - Have measurable disease based on RECIST 1.1. - Have adequate organ function. Exclusion Criteria: - Prior treatment with immune checkpoint inhibitors. - For female participants: pregnancy or planned pregnancy. - The unavailability of the tumor or serial liquid biopsy samples.

Study Design


Locations

Country Name City State
Russian Federation N.N.Blokhin National Medical Research Center of Oncology Moscow
Russian Federation State Budgetary Institution of Healthcare of the City of Moscow "Moscow Multidisciplinary Clinical Center "Kommunarka" of the Department of Health of the City of Moscow Moscow

Sponsors (3)

Lead Sponsor Collaborator
OncoAtlas LLC Moscow MultidisciplinaryClinical Center Kommunarka, N.N. Blokhin National Medical Research Center of Oncology

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type Measure Description Time frame Safety issue
Other Correlation of biomarkers with the treatment outcomes Dynamics of biomarkers in serial liquid biopsy samples will be correlated with treatment outcomes. Response to treatment will be determined by RECIST v1.1. Through study completion, an average of 3 years
Other Evaluation of the ctDNA dynamics in the course of ICI in serial plasma samples Dynamics of ctDNA in serial liquid biopsy samples will be correlated with treatment outcomes. Response to treatment will be determined by RECIST v1.1. Through study completion, an average of 3 years
Primary Concordance of NGS and routine methods (PCR, IHC) for MSI analysis Concordance will be calculated using Cohen's Kappa (?) Through study completion, an average of 3 years
Secondary Concordance of MSI in tumor tissue and liquid biopsy (ctDNA) Concordance will be calculated using Cohen's Kappa (?) Through study completion, an average of 3 years
Secondary Qualitative and quantitative status of MSI in serial liquid biopsy (ctDNA) samples Liquid biopsy samples will be collected prior to the start of ICI, on the 14th and 28th days of therapy and at every follow-up tumor scan Through study completion, an average of 3 years
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