Dynamics of MSI and Genomic Profile of Colorectal Cancer In the Course of Immune Checkpoint Inhib… (NCT06414304) | Clinical Trial Compass
CompletedNot Applicable
Dynamics of MSI and Genomic Profile of Colorectal Cancer In the Course of Immune Checkpoint Inhibitor Therapy
Russia30 participantsStarted 2022-06-01
Plain-language 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.
Who can participate
Age range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
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.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Concordance of NGS and routine methods (PCR, IHC) for MSI analysis
Timeframe: Through study completion, an average of 3 years