CfDNA in Hereditary And High-risk Malignancies 2

ConditionHereditary Cancer Syndrome

Trial statusRecruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

AgeUp to 90

SponsorUniversity Health Network, Toronto

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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 population

The population to be studied includes: Any individual that underwent clinical genetic testing for hereditary breast and ovarian cancer syndrome, Lynch Syndrome, Neurofibromatosis Type 1, Li-Fraumeni Syndrome or Hereditary Diffuse Gastric Cancer, and was found to carry a detectable variant that is likely pathogenic or pathogenic.

Trial design

Design model

Case-control

Time perspective

Prospective

Treatments tested in this trial

Cell-free DNA analysis
Diagnostic test
Analysis of cell-free DNA in blood plasma will involve targeted sequencing of key cancer-related genes, cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq), and shallow whole genome sequencing (sWGS).

Treatment groups

1,000 Participants

are divided into 2 treatment groups

Group A: Test cohort1 intervention

Group B: Control0 interventions

Trial outcomes

Primary outcomes

Determine the cancer detection rate of the cfDNA sequencing assay in patients with HCS.

The investigators will assess the performance of the cfDNA assay for cancer detection in patients with HCS, including assay sensitivity, specificity, positive predictive value (PPV,) and negative predictive value (NPV). The test performance endpoint is a diagnosis of cancer and will be assessed at multiple points during the study (at a minimum yearly).

Time frame