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NCT Number: NCT06726642

CfDNA in Hereditary And High-risk Malignancies 2

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.

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Key information

Conditions

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

Age range

Up to 90 year

Sex eligibility

All sexes

Study type

Observational

Primary location

BC Cancer Agency, Vancouver, British Columbia, Canada

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Cell-free DNA analysis

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).

Primary outcomes

  1. 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).

Secondary outcomes

  1. 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.

  2. 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).

  3. 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. 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).

  5. 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).

Study contacts

Contact information is provided by the study sponsor or research team.

Julia Sobotka, MSc

CONTACT

[email protected]

416-409-1387

Sponsors and collaborators

Lead sponsor

University Health Network, Toronto

Other

Collaborators

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

Registry information

Official study title

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

Acronym: CHARM2

Important dates

Study start
2024
Primary completion
2029
Study completion
2031
First posted
Dec 10, 2024
Registry last updated
Dec 16, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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