Cell-free DNA in Hereditary And High-Risk Malignancies

Study Overview
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Brief Summary
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The goal of this study is to develop an effective, sensitive blood test that can detect early tumours in patients with known or suspected hereditary cancer syndromes (HCS). 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 also use questionnaires and interviews to understand how patients feel about incorporating these tests into routine medical care, and the perceptions of the medical value of test results.

Detailed Description
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The objective of this protocol is to develop a method to detect early signs of cancer in 'previvors' (people with HCS that do not yet have a cancer diagnosis). This will enable prediction of cancer onset so that patients and their doctors can make decisions to treat or prevent the cancers. HCS patients will be recruited from across Canada to provide blood samples before and after cancer diagnosis. In parallel, there will be development of a circulating tumour DNA (ctDNA) -based test to detect early stage cancer and evaluation on the cost-effectiveness and feasibility of integrating such screening protocols into routine clinical care. In concert, consultation with patients and health care providers will occur to create recommendations for use within clinical care.

Official Title
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Early Detection of Cancer in High-risk Patients Through Cell-free DNA

Conditions
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Hereditary Cancer Syndrome

Intervention / Treatment
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* Genetic: Next generation sequencing (NGS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individual with any known or suspected hereditary cancer predisposition (i.e. individuals with an identified pathogenic or likely pathogenic variant in a cancer predisposition gene and/or a family history of cancer without an identified gene mutation) at any stage in their cancer journey (ie: cancer survivor, unaffected with cancer, current cancer patient). Individual must be greater than 18 years of age Individual must speak English or French to participate in the qualitative interview and/or survey Exclusion Criteria: 1. Individuals that do not meet the outlined inclusion criteria.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CHARM<br>Patients identified with hereditary breast and ovarian cancer syndrome (germline BRCA1 or BRCA2 carrier) or Lynch syndrome (germline variant in EPCAM, MLH1, MSH2, MSH6, or PMS2). | Genetic: Next generation sequencing (NGS)<br>* NGS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Collection of biospecimens from 1500 HSC carriers. | Facilitate and streamline the collection, banking, and annotation of plasma samples and tumour tissue (if applicable) across Canada. | up to 4 years | 
| Collection of clinical data from 1500 HSC carriers. | Extract clinical data for all study participants from electronic medical records. Data collection will include family history and medical history. | up to 4 years | 
| Detection of early stage cancer in HCS patients using cfDNA. | Detect concentration of cfDNA circulating in the blood by shallow whole-genome sequencing, targeted panel analysis, and cfMeDIP. | up to 4 years | 
| Evaluation of the clinical utility of a cfDNA test for HSC patients. | Conduct qualitative interviews with healthcare providers and patients. | up to 4 years | 
| Evaluation of the optimal implementation of cfDNA in clinical practice. | Conduct a discrete choice experiment survey with HCS patient and providers. | up to 4 years | 
| Evaluation of cfDNA test implementation through cost-effectiveness analysis of cfDNA versus standard of care. | Conduct economic modelling using the economic evaluation guidelines from the Canadian Agency for Drugs and Technologies in Health. | up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Circulating tumour DNA, Cell-free DNA (cfDNA), Hereditary cancer syndrome, Cancer, BRCA1, Lynch syndrome, Hereditary breast and ovarian cancer, Liquid biopsies, BRCA2