Cell-free DNA in Hereditary And High-Risk Malignancies (CHARM)

• ClinicalTrials.gov Identifier: NCT04261972
• Recruitment Status: Recruiting
• First Posted: February 10, 2020
• Last Update Posted: February 15, 2022
• Sponsor: University Health Network, Toronto
• Collaborators: Sinai Health System; Women's College Hospital; British Columbia Cancer Agency; Jewish General Hospital; IWK Health Centre; Eastern Health
• Information provided by (Responsible Party): University Health Network, Toronto

Tracking Information

• First Submitted Date: January 2, 2020
• First Posted Date: February 10, 2020
• Last Update Posted Date: February 15, 2022
• Actual Study Start Date: July 1, 2018
• Estimated Primary Completion Date: October 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 7, 2020)

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

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cell-free DNA in Hereditary And High-Risk Malignancies
• Official Title: Early Detection of Cancer in High-risk Patients Through Cell-free DNA
• 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.
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

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.

• 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.

• Condition: Hereditary Cancer Syndrome

Intervention

Genetic: Next generation sequencing (NGS)

NGS

Study Groups/Cohorts

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).

Intervention: Genetic: Next generation sequencing (NGS)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 7, 2020): 1500
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2023
• Estimated Primary Completion Date: October 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. 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).
2. Individual must be greater than 18 years of age
3. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Leslie Oldfield, MSc.; 613-532-9847; charm@uhnresearch.ca

• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT04261972
• Other Study ID Numbers: 1655
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: University Health Network, Toronto
• Original Responsible Party: Same as current
• Current Study Sponsor: University Health Network, Toronto
• Original Study Sponsor: Same as current

Collaborators

• Sinai Health System
• Women's College Hospital
• British Columbia Cancer Agency
• Jewish General Hospital
• IWK Health Centre
• Eastern Health

Investigators

• Principal Investigator: Raymond Kim, MD; Princess Margaret Cancer Centre

• PRS Account: University Health Network, Toronto
• Verification Date: February 2022