Ignite Creation Date:
2024-05-19 @ 5:34 PM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06414304
Status:
RECRUITING
Last Update Posted:
2024-05-16
First Post:
2024-05-07
Brief Title:
Dynamics of MSI and Genomic Profile of Colorectal Cancer In the Course of Immune Checkpoint Inhibitor Therapy
Sponsor:
OncoAtlas LLC
Organization:
OncoAtlas LLC
Study Overview
Official Title:
A Multi-center Observational Clinical Trial Evaluating the Dynamics of Microsatellite Instability and Genomic Profile of Colorectal Cancer in the Course of Treatment With Immune Checkpoint Inhibitors
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BLOOMSI
Brief 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 MSIdMMR 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 pV600E 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
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 pV600E 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
Detailed 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 MSIdMMR-positive tumors who are candidates for the ICI treatment will be included in the study MSIdMMR 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 andor 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 v11
Patients with MSIdMMR-positive tumors who are candidates for the ICI treatment will be included in the study MSIdMMR 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 andor 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 v11
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 22-75-10154 | OTHER_GRANT | Russian Science Foundation | None |