CfDNA in Hereditary And High-risk Malignancies 2

NCT ID: NCT06726642

Last Updated: 2025-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

1000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-04-19

Study Completion Date

2031-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Hereditary Cancer Syndrome

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Cell-free DNA analysis

Intervention Type DIAGNOSTIC_TEST

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.

No interventions assigned to this group

Interventions

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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).

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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).
Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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British Columbia Cancer Agency

OTHER

Sponsor Role collaborator

Eastern Health

OTHER

Sponsor Role collaborator

IWK Health Centre

OTHER

Sponsor Role collaborator

Jewish General Hospital

OTHER

Sponsor Role collaborator

Sinai Health System

OTHER

Sponsor Role collaborator

The Hospital for Sick Children

OTHER

Sponsor Role collaborator

University of Alberta

OTHER

Sponsor Role collaborator

Women's College Hospital

OTHER

Sponsor Role collaborator

University Health Network, Toronto

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Raymond Kim, MD

Role: PRINCIPAL_INVESTIGATOR

Princess Margaret Cancer Centre

Locations

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BC Cancer Agency

Vancouver, British Columbia, Canada

Site Status NOT_YET_RECRUITING

Eastern Health

St. John's, Newfoundland and Labrador, Canada

Site Status NOT_YET_RECRUITING

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status NOT_YET_RECRUITING

The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status NOT_YET_RECRUITING

Sinai Health System

Toronto, Ontario, Canada

Site Status RECRUITING

University Health Network

Toronto, Ontario, Canada

Site Status RECRUITING

Women's College Hospital

Toronto, Ontario, Canada

Site Status NOT_YET_RECRUITING

Jewish General Hospital

Montreal, Quebec, Canada

Site Status NOT_YET_RECRUITING

Countries

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Canada

Central Contacts

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Julia Sobotka, MSc

Role: CONTACT

416-409-1387

Facility Contacts

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Intan Schrader, MD

Role: primary

604-877-6000 ext. Ext. 672198

Sara Singh

Role: backup

Lesa Dawson

Role: primary

709-749-9686

Stacy Whittle

Role: backup

Lynette Penney, MD

Role: primary

902-470-8754

Ann Gong

Role: primary

416-813-8204

David Malkin, MD

Role: backup

416-813-5348 ext. Ex 305348

Raymond Kim, MD

Role: primary

416-586-4800 ext. Ext. 4220

Raymond Kim, MD

Role: primary

416-586-4800 ext. Ext. 4220

Julia Sobotka, MSc

Role: backup

Gabby Ene

Role: primary

(416)-946-4501 ext. Ext. 3969

William Foulkes, MD

Role: primary

514-934-1934 ext. Ext 44121

Mark Basik, MD

Role: backup

References

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Farncombe KM, Wong D, Norman ML, Oldfield LE, Sobotka JA, Basik M, Bombard Y, Carile V, Dawson L, Foulkes WD, Malkin D, Karsan A, Parkin P, Penney LS, Pollett A, Schrader KA, Pugh TJ, Kim RH; CHARM consortium. Current and new frontiers in hereditary cancer surveillance: Opportunities for liquid biopsy. Am J Hum Genet. 2023 Oct 5;110(10):1616-1627. doi: 10.1016/j.ajhg.2023.08.014.

Reference Type BACKGROUND
PMID: 37802042 (View on PubMed)

Related Links

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https://charmconsortium.ca/about/

CHARM consortium website

Other Identifiers

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23-5766

Identifier Type: -

Identifier Source: org_study_id