Cell-free DNA in Hereditary And High-Risk Malignancies 1

NCT04261972 | Active Not Recruiting

• 1 other identifier: 1655
• Study Type: observational
• Target: 1,416
• Locations: 1 country
• Sites: 7

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.

Conditions

Hereditary Cancer Syndrome

Keywords

Circulating tumour DNA; Cell-free DNA (cfDNA); Hereditary cancer syndrome; Cancer; BRCA1; Lynch syndrome; Hereditary breast and ovarian cancer; Liquid biopsies; BRCA2

Outcome Measures

Primary Outcomes (6)

• 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

Study Arms (1)

CHARM

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)

Interventions

Next generation sequencing (NGS) GENETIC

NGS

CHARM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The population to be studied includes: 1. Any individual that underwent clinical genetic testing for hereditary breast and ovarian cancer syndrome or Lynch Syndrome and was found to carry a detectable variant that is likely pathogenic or pathogenic. 2. Any individual with a suspected cancer predisposition that has not yet received genetic testing. 3. Any individual who received negative genetic test results but has a strong personal or family history of cancer.

You may qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Sinai Health System: collaborator
• Women's College Hospital: collaborator
• Jewish General Hospital: collaborator
• IWK Health Centre: collaborator
• British Columbia Cancer Agency: collaborator
• Eastern Health: collaborator

Study Sites (7)

BC Cancer Agency

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Eastern Health

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

Sinai Health System

Toronto, Ontario, M5G 1X5, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Women's College Hospital

Toronto, Ontario, M5S 1B2, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Biospecimen

Retention: SAMPLES WITH DNA

Longitudinal blood plasma collected annually on patients. Archived formalin-fixed paraffin-embedded tissue or fresh frozen tissue from a biopsy or surgery is collected when applicable.

MeSH Terms

Conditions

Neoplastic Syndromes, Hereditary; Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis; Hereditary Breast and Ovarian Cancer Syndrome

Interventions

High-Throughput Nucleotide Sequencing

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Breast Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Officials

• Raymond Kim, MD

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2020
• First Posted: February 10, 2020
• Study Start: July 1, 2018
• Primary Completion: December 31, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 14, 2026

Record last verified: 2026-01

Locations

CA (7)