## Protocol Section
### Identification Module
**NCT ID:** NCT06414304

**Acronym:** BLOOMSI

**Brief Title:** Dynamics of MSI and Genomic Profile of Colorectal Cancer In the Course of Immune Checkpoint Inhibitor Therapy

**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

#### Organization Study ID Info
**ID:** BLOOMSI
#### Organization
**Class:** INDUSTRY
**Full Name:** OncoAtlas LLC
#### Secondary ID Infos
**Domain:** Russian Science Foundation
**ID:** 22-75-10154
**Type:** OTHER_GRANT
### Status Module
#### Completion Date
**Date:** 2026-07

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-13

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-07

**Type:** ESTIMATED

#### Start Date
**Date:** 2022-06-01

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-07
**Study First Submit QC Date:** 2024-05-13
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** N.N. Blokhin National Medical Research Center of Oncology

**Class:** UNKNOWN

**Name:** Moscow MultidisciplinaryClinical Center Kommunarka

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** OncoAtlas LLC

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**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 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.

**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 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.

### Conditions Module

**Conditions:**

- Colorectal Cancer

- Colorectal Cancer Metastatic

- MSI-H Colorectal Cancer

- dMMR Colorectal Cancer

- Cancer

- Colon Adenocarcinoma

**Keywords:**

- MSI

- dMMR

- Microsatellite instability

- Next-generation sequencing

- Immunotherapy

- Immune checkpoint inhibitors

- Colorectal cancer

### Design Module

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 70

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Outcomes Module

#### Other Outcomes

**Description:** Dynamics of biomarkers in serial liquid biopsy samples will be correlated with treatment outcomes. Response to treatment will be determined by RECIST v1.1.

**Measure:** Correlation of biomarkers with the treatment outcomes

**Time Frame:** Through study completion, an average of 3 years

**Description:** Dynamics of ctDNA in serial liquid biopsy samples will be correlated with treatment outcomes. Response to treatment will be determined by RECIST v1.1.

**Measure:** Evaluation of the ctDNA dynamics in the course of ICI in serial plasma samples

**Time Frame:** Through study completion, an average of 3 years

#### Primary Outcomes

**Description:** Concordance will be calculated using Cohen's Kappa (κ)

**Measure:** Concordance of NGS and routine methods (PCR, IHC) for MSI analysis

**Time Frame:** Through study completion, an average of 3 years

#### Secondary Outcomes

**Description:** Concordance will be calculated using Cohen's Kappa (κ)

**Measure:** Concordance of MSI in tumor tissue and liquid biopsy (ctDNA)

**Time Frame:** Through study completion, an average of 3 years

**Description:** 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

**Measure:** Qualitative and quantitative status of MSI in serial liquid biopsy (ctDNA) samples

**Time Frame:** Through study completion, an average of 3 years

### Eligibility Module

**Eligibility Criteria:** 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.

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Patients with histologically confirmed colorectal cancer with microsatellite instability (MSI) or mismatch repair deficiency (dMMR)

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** maxim.ivanov@oncoatlas.ru

**Name:** Maxim Ivanov, PhD

**Phone:** +7 909 677-52-74

**Role:** CONTACT

**Contact 2:**

**Email:** lebedeva@oncoatlas.ru

**Name:** Alexandra Lebedeva, MSc

**Phone:** +7 915 417-36-77

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Moscow

**Contacts:**

***Contact 1:***

- **Name:** Olesya Kuznetsova, MD

- **Role:** CONTACT

**Country:** Russian Federation

**Facility:** N.N.Blokhin National Medical Research Center of Oncology

**Status:** RECRUITING

**Zip:** 115478

**Location 2:**

**City:** Moscow

**Contacts:**

***Contact 1:***

- **Name:** Mikhail Fedyanin, MD, PhD

- **Role:** CONTACT

**Country:** Russian Federation

**Facility:** 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

**Status:** RECRUITING

**Zip:** 142770

#### Overall Officials

**Official 1:**

**Affiliation:** OncoAtlas LLC

**Name:** Maxim Ivanov, PhD

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000007414

- Term: Intestinal Neoplasms

- ID: D000005770

- Term: Gastrointestinal Neoplasms

- ID: D000004067

- Term: Digestive System Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000005767

- Term: Gastrointestinal Diseases

- ID: D000003108

- Term: Colonic Diseases

- ID: D000007410

- Term: Intestinal Diseases

- ID: D000012002

- Term: Rectal Diseases

- ID: D000042822

- Term: Genomic Instability

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BC06

- Name: Digestive System Diseases

### Condition Browse Module - Browse Leaves

- ID: M3585

- Name: Adenocarcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M27510

- Name: Microsatellite Instability

- Relevance: HIGH

- As Found: Microsatellite Instability

- ID: M17890

- Name: Colorectal Neoplasms

- Relevance: HIGH

- As Found: Colorectal Cancer

- ID: M6338

- Name: Colonic Neoplasms

- Relevance: HIGH

- As Found: Colon Adenocarcinoma

- ID: M10448

- Name: Intestinal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8886

- Name: Gastrointestinal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7256

- Name: Digestive System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6336

- Name: Colonic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10444

- Name: Intestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14844

- Name: Rectal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M25088

- Name: Genomic Instability

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000015179

- Term: Colorectal Neoplasms

- ID: D000003110

- Term: Colonic Neoplasms

- ID: D000053842

- Term: Microsatellite Instability

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M2342

- Name: Immune Checkpoint Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M2853

- Name: Immunomodulating Agents

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
