CfDNA in Hereditary And High-risk Malignancies 2

Recruiting

• Conditions: Hereditary Cancer Syndrome

• Registration Number: NCT06726642
• Lead Sponsor: University Health Network, Toronto

Brief Summary

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

Through the CHARM Consortium (www.charmconsortium.ca), we have shown that cell-free DNA (cfDNA) profiling can enable more frequent cancer surveillance from readily accessible blood collections. We 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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2024-04-19
• Study First Submitted: 2024-11-08
• Status Verified: 2024-12
• Study First Submitted QC: 2024-12-09
• Last Update Submitted: 2024-12-09
• Study First Posted: 2024-12-10
• Last Update Posted: 2024-12-10
• Primary Completion: 2029-12
• Study Completion: 2031-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

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.

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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).

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Determine the cancer detection rate of the cfDNA sequencing assay in patients with HCS.	4 years from enrollment in the study.	We will assess the performance of the cfDNA assay for cancer detection in patients with HCS, including assay sensitivity, specificity, PPV, and NPV. The test performance endpoint is a diagnosis of cancer and will be assessed at multiple points during the study (at a minimum yearly).

Secondary Outcome Measures

Name	Time	Method
To assess the time to cancer diagnosis using cfDNA sequencing compared to controls.	4 years from enrollment in the study.	We 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. We will also assess the time to disease management in carriers receiving cfDNA sequencing results compared to controls.
To assess the detection rate of cancers with no standard-of-care screening available using cfDNA sequencing.	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 protocols (e.g., pancreatic cancer, endometrial cancer).
Assess the impact of tri-annual cfDNA testing on participant cancer worry.	4 years from enrollment in the study.	We will assess the impact of tri-annual cfDNA testing on participants' cancer related worry, using the Cancer Worry Scale (PMID: 19382100).
Assess the impact of tri-annual cfDNA testing on cancer risk perception.	4 years from enrollment in the study.	We will assess the impact of tri-annual cfDNA testing on participants' risk perception, using the Multidimensional Impact of Cancer Risk Assessment (PMID: 12433008).
Assess the impact of tri-annual cfDNA testing on cancer anxiety and depression.	4 years from enrollment in the study.	We will assess the impact of tri-annual cfDNA testing on participants' anxiety and depression using the Hospital Anxiety and Depression Scale (PMID: 18325093).

Trial Locations

Locations (8)

BC Cancer Agency; 🇨🇦 Vancouver, British Columbia, Canada

Eastern Health; 🇨🇦 St. John's, Newfoundland and Labrador, Canada

IWK Health Centre; 🇨🇦 Halifax, Nova Scotia, Canada

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada

Sinai Health System; 🇨🇦 Toronto, Ontario, Canada

University Health Network; 🇨🇦 Toronto, Ontario, Canada

Women's College Hospital; 🇨🇦 Toronto, Ontario, Canada

Jewish General Hospital; 🇨🇦 Montreal, Quebec, Canada