CfDNA in Hereditary And High-risk Malignancies 2 (CHARM2)

December 8, 2025 updated by: University Health Network, Toronto

CfDNA in Hereditary And High-risk Malignancies (CHARM) 2: Evaluating the Performance of a cfDNA Blood Test for Early Cancer Detection

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Through the CHARM Consortium (www.charmconsortium.ca), the investigators have shown that cell-free DNA (cfDNA) profiling can enable more frequent cancer surveillance from readily accessible blood collections. The investigators are now conducting a prospective, multi-center, randomized control trial of cfDNA testing of 1,000 HCS carriers from across Canada to 1) compare cancer detection rates with and without cfDNA testing, 2) assess cancer stage shift and clinical impact reducing mortality and morbidity cancers, and 3) assess impact of access to cfDNA results on patients' quality of life and psychological distress.

Study Type

Observational

Enrollment (Estimated)

1000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Julia Sobotka, MSc
  • Phone Number: 416-409-1387
  • Email: charm@uhn.ca

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3K 6R8
        • Not yet recruiting
        • IWK Health Centre
        • Principal Investigator:
          • Lynette Penney, MD
        • Contact:
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • University Health Network
        • Principal Investigator:
          • Raymond Kim, MD
        • Contact:
        • Contact:
      • Toronto, Ontario, Canada, M5G 1X5
        • Recruiting
        • Sinai Health System
        • Principal Investigator:
          • Raymond Kim, MD
        • Contact:
      • Toronto, Ontario, Canada, M5S 1B2
        • Not yet recruiting
        • Women's College Hospital
        • Principal Investigator:
          • Michelle Jacobson, MD
        • Contact:
      • Toronto, Ontario, Canada, M5G 1E8
        • Not yet recruiting
        • The Hospital for Sick Children
        • Contact:
        • Contact:
        • Principal Investigator:
          • David Malkin, MD
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Not yet recruiting
        • Jewish General Hospital
        • Principal Investigator:
          • William Foulkes, MD
        • Principal Investigator:
          • Mark Basik, MD
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study 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.

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Test cohort
All participants in the experimental cohort will provide blood samples tri-annually (every 4 months) for 4 years, either at the study hospital or at a local blood laboratory (e.g., LifeLabs). Whenever possible, patients will have research blood collected at the same time as routine blood collections for clinical purposes to avoid additional venipunctures. The samples will undergo cfDNA analysis and all results will be returned to participants by the study team. Participants who receive a "positive" cfDNA assay result will be offered follow-up diagnostic procedures to confirm or rule out the presence of a malignancy. Participants will also complete questionnaires and semi-structured interviews to explore their experience with cfDNA testing and understand perceptions of the clinical utility of cfDNA tests for HCS management.
Diagnostic test: Cell-free DNA analysis
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).
Control
Participants in the control cohort will not receive the cfDNA blood test and will continue to receive standard-of-care cancer surveillance according to current guidelines, as they were prior to study enrollment. Participants will complete questionnaires and semi-structured interviews to explore their experience with cfDNA testing and to understand their perception of the clinical utility of cfDNA tests for HCS management.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the cancer detection rate of the cfDNA sequencing assay in patients with HCS.
Time Frame: 4 years from enrollment in the study.
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).
4 years from enrollment in the study.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To assess the time to cancer diagnosis using cfDNA sequencing compared to controls.
Time Frame: 4 years from enrollment in the study.
The investigators will establish whether blood plasma cfDNA testing can detect cancers at the same time as, or earlier, than conventional standard-of-care screening tests for carriers of HCS. The investigators will also assess the time to disease management in carriers receiving cfDNA sequencing results compared to controls.
4 years from enrollment in the study.
To assess the detection rate of cancers with no standard-of-care screening available using cfDNA sequencing.
Time Frame: 4 years from enrollment in the study.
To establish whether cfDNA testing increases the frequency of cancers detected, in particular cancer types with limited detection rates using standard-of-care (e.g., pancreatic cancer, endometrial cancer).
4 years from enrollment in the study.
Assess the impact of tri-annual cfDNA testing on participant cancer worry.
Time Frame: 4 years from enrollment in the study.
The investigators will assess the impact of tri-annual cfDNA testing on participants' cancer related worry, using the Cancer Worry Scale (PMID: 19382100).
4 years from enrollment in the study.
Assess the impact of tri-annual cfDNA testing on cancer risk perception.
Time Frame: 4 years from enrollment in the study.
The investigators will assess the impact of tri-annual cfDNA testing on participants' risk perception, using the Multidimensional Impact of Cancer Risk Assessment (PMID: 12433008).
4 years from enrollment in the study.
Assess the impact of tri-annual cfDNA testing on cancer anxiety and depression.
Time Frame: 4 years from enrollment in the study.
The investigators will assess the impact of tri-annual cfDNA testing on participants' anxiety and depression using the Hospital Anxiety and Depression Scale (PMID: 18325093).
4 years from enrollment in the study.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Collaborators

The Hospital for Sick Children
University of Alberta
Women's College Hospital
Jewish General Hospital
IWK Health Centre
British Columbia Cancer Agency
Sinai Health System
Eastern Health

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 19, 2024

Primary Completion (Estimated)

December 1, 2029

Study Completion (Estimated)

December 1, 2031

Study Registration Dates

First Submitted

November 8, 2024

First Submitted That Met QC Criteria

December 9, 2024

First Posted (Actual)

December 10, 2024

Study Record Updates

Last Update Posted (Actual)

December 16, 2025

Last Update Submitted That Met QC Criteria

December 8, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23-5766

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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