Cell-free DNA in Hereditary And High-Risk Malignancies

Active, not recruiting

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
CHARM	Next generation sequencing (NGS)	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).

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method

Locations (7): BC Cancer Agency
🇨🇦
Vancouver, British Columbia, Canada
Sinai Health System
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Toronto, Ontario, Canada
IWK Health Centre
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Halifax, Nova Scotia, Canada
Jewish General Hospital
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Montreal, Quebec, Canada
Eastern Health
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St. John's, Newfoundland and Labrador, Canada
Women's College Hospital
🇨🇦
Toronto, Ontario, Canada
University Health Network
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Toronto, Ontario, Canada