CfDNA in Hereditary And High-risk Malignancies 2 (CHARM2)

University Health Network, Toronto

Status: Enrolling

Conditions: Hereditary Cancer Syndrome

Treatments: Diagnostic Test: Cell-free DNA analysis

Study type: Observational

Funder types: Other

Identifiers

NCT06726642

23-5766

Details and patient eligibility

About

The goal of this study is to understand the performance of an experimental blood test that aims to detect early tumors in patients with hereditary cancer syndromes. If this new blood test is accurate, it could be used to screen patients for cancer and allow for earlier cancer detection. The study will compare cancer detection rates between those receiving the new blood test and those receiving standard care, assess if the test leads to earlier cancer diagnosis, and evaluate its impact on patient outcomes. The study will also use questionnaires and interviews to understand how patients feel about the blood test, its incorporation into routine medical care, and perceptions of the medical value of test results. This research could lead to more effective and less invasive cancer screening for high-risk individuals.

Full description

Through the CHARM Consortium (www.charmconsortium.ca), we have shown that cell-free DNA (cfDNA) profiling can enable more frequent cancer surveillance from readily accessible blood collections. We are now conducting a prospective, multi-center, randomized control trial of cfDNA testing of 1,000 HCS carriers from across Canada to 1) compare cancer detection rates with and without cfDNA testing, 2) assess cancer stage shift and clinical impact reducing mortality and morbidity cancers, and 3) assess impact of access to cfDNA results on patients' quality of life and psychological distress.

Enrollment: 1,000 estimated patients

Sex: All

Ages: Under 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with a confirmed diagnosis of hereditary breast and ovarian cancer (HBOC), Lynch Syndrome (LS), Neurofibromatosis type I (NF1), Li-Fraumeni Syndrome (LFS), PALB2, and Hereditary Diffuse Gastric Cancer (HDGC), (i.e., patients with an identified pathogenic variant in the respective cancer predisposition gene, or patients with uninformative genetic testing but with a family history suggestive of the cancer predisposition syndrome).
• Patients must be receiving standard-of-care clinical assessment for cancer by a managing physician under a provincial screening program or cancer surveillance protocol.
• All patients must have signed and dated an informed consent form for this study.

Exclusion criteria

• Patients must not have a personal history of cancer diagnosed and treated within 3 years prior to the expected first sample collection date for this study. If a patient has a personal history of cancer, treatment must have been completed successfully at least 3 years prior to first study sample collection.
• Patients diagnosed more than 3 years prior to the expected first sample collection date, but never been treated for the cancer.
• Patients undergoing investigations for a clinical suspicion of cancer.
• Patients who are not able to comply with the protocol (i.e., tri-annual blood sample collection if randomized into the experimental cohort).

Trial design

1,000 participants in 2 patient groups

Test cohort

Description:

All participants in the experimental cohort will provide blood samples tri-annually (every 4 months) for 4 years, either at the study hospital or at a local blood laboratory (e.g., LifeLabs). Whenever possible, patients will have research blood collected at the same time as routine blood collections for clinical purposes to avoid additional venipunctures. The samples will undergo cfDNA analysis and all results will be returned to participants by the study team. Participants who receive a "positive" cfDNA assay result will be offered follow-up diagnostic procedures to confirm or rule out the presence of a malignancy. Participants will also complete questionnaires and semi-structured interviews to explore their experience with cfDNA testing and understand perceptions of the clinical utility of cfDNA tests for HCS management.

Treatment:

Diagnostic Test: Cell-free DNA analysis

Control

Description:

Participants in the control cohort will not receive the cfDNA blood test and will continue to receive standard-of-care cancer surveillance according to current guidelines, as they were prior to study enrollment. Participants will complete questionnaires and semi-structured interviews to explore their experience with cfDNA testing and to understand their perception of the clinical utility of cfDNA tests for HCS management.