Understanding the immune response in Lynch syndrome patients

Impact of Immune-surveillance on the Development of Colorectal Cancer in Patients With Lynch Syndrome

This study is trying to see if certain antibodies in the immune system can help spot early signs of cancer in people with Lynch syndrome.

Quick facts

• Study type: Observational
• Enrollment: 300 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: San Raffaele University (other)
• Locations: 5 sites (Monrovia, California and 4 other locations)
• Trial ID: NCT06708429 on ClinicalTrials.gov

What this trial studies

This observational study investigates the relationship between the immune system and the enteral mucosa in individuals with Lynch syndrome, a genetic condition that significantly increases the risk of colorectal and endometrial cancers. It aims to identify anti-frame-shift peptide antibodies as potential early biomarkers for cancer development in these patients. By employing a retro-prospective design, the study seeks to explore the biological processes that lead to interval colorectal cancers, which occur despite regular surveillance. Participants will include those with Lynch syndrome as well as healthy controls and patients with sporadic colorectal lesions.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 18 and older with a confirmed diagnosis of Lynch syndrome and a pathogenic variant in specific genes.

Not a fit: Patients without Lynch syndrome or those with sporadic colorectal lesions may not benefit from the findings of this study.

Why it matters

Potential benefit: If successful, this study could lead to earlier identification of patients at high risk for developing colorectal cancer, potentially improving surveillance and treatment strategies.

How similar studies have performed: While previous studies have explored anti-frame-shift peptide antibodies in a cross-sectional manner, this retro-prospective approach is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria (for participants with Lynch syndrome):

* Age ≥18 years
* All sexes eligible
* Established diagnosis of Lynch syndrome performed as part of clinical practice, with a germline pathogenic/likely pathogenic variant in one of the following genes: MLH1, MSH2, MSH6, PMS2, and EpCAM
* Subjects with Lynch syndrome undergoing surveillance gastrointestinal endoscopy and/or surgery according to clinical practice
* Fertile patients (both males and females) are eligible
* Lactating women are eligible

Inclusion Criteria (for participants without Lynch syndrome):

* Age ≥18 years
* All sexes eligible
* Patients with sporadic colorectal lesions, including colorectal cancer and colorectal adenomas
* Healthy controls without colorectal cancer or adenomas undergoing lower gastrointestinal endoscopy for abdominal pain
* PREMM5 \< 2.5 \[PREMM5 is an online, free-to-use, clinical prediction algorithm that estimates the cumulative probability of an individual carrying a germline mutation in the mismatch repair genes responsible for Lynch syndrome\].

Exclusion Criteria (for participants with or without Lynch syndrome):

* Age \< 18 years;
* Diseases that are known to predispose to colorectal cancer (personal past or recent history of inflammatory bowel disease);
* Patients unable/unwilling to provide consent;
* Pregnancy

Where this trial is running

Monrovia, California and 4 other locations

• Beckman Research Institute at City of Hope — Monrovia, California, United States (RECRUITING)
• Gastronterology and Gastrointestinal Endoscopy Unit, IRCCS San Raffaele Hospital — Milan, Lombardy, Italy (RECRUITING)
• Dipartimento di Chirurgia Oncologica e Dipartimento di Oncologia Sperimentale Istituto Nazionale Tumori — Milan, MI, Italy (RECRUITING)
• Dipartimento di controllo qualità e rischio chimico biologico, AOOR Villa Sofia Cervello — Palermo, PM, Italy (RECRUITING)
• Chirurgia Generale, Azienda Ospedaliero Universitaria di Cagliari — Cagliari, Italy (RECRUITING)

Study contacts

• Principal investigator: Giulia Martina Cavestro, MD, PhD — IRCCS San Raffaele Scientific Institute
• Study coordinator: Giulia Martina Cavestro, MD, PhD

Conditions: Lynch Syndrome, Lynch Syndrome I, Lynch Syndrome II, HNPCC, HNPCC Gene Mutation, Hereditary Cancer Syndrome, Hereditary Cancer, MLH1 Gene Mutation