CfDNA in Hereditary And High-risk Malignancies 2

NCT06726642 | Recruiting DMC

• 1 other identifier: 23-5766
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 8

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.

Conditions

Hereditary Cancer Syndrome

Keywords

cfDNA; cell-free DNA; Hereditary cancer syndrome; BRCA1; BRCA2; Lynch Syndrome; Hereditary breast and ovarian cancer (HBOC); Liquid biopsy; Circulating tumor DNA; Hereditary Diffuse Gastric Cancer (HDGC); Li-Fraumeni syndrome

Outcome Measures

Primary Outcomes (1)

• Determine the cancer detection rate of the cfDNA sequencing assay in patients with HCS.

  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 Outcomes (5)

• To assess the time to cancer diagnosis using cfDNA sequencing 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.

  4 years from enrollment in the study.

• Assess the impact of tri-annual cfDNA testing on participant cancer worry.

  4 years from enrollment in the study.

• Assess the impact of tri-annual cfDNA testing on cancer risk perception.

  4 years from enrollment in the study.

• Assess the impact of tri-annual cfDNA testing on cancer anxiety and depression.

  4 years from enrollment in the study.

Study Arms (2)

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

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.

Interventions

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).

Test cohort

Eligibility Criteria

• Age: Up to 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

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

Study Sites (8)

BC Cancer Agency

Vancouver, British Columbia, V5Z 4E6, Canada

NOT YET RECRUITING

Eastern Health

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

NOT YET RECRUITING

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

NOT YET RECRUITING

The Hospital for Sick Children

Toronto, Ontario, M5G 1E8, Canada

NOT YET RECRUITING

Sinai Health System

Toronto, Ontario, M5G 1X5, Canada

RECRUITING

University Health Network

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Women's College Hospital

Toronto, Ontario, M5S 1B2, Canada

NOT YET RECRUITING

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

NOT YET RECRUITING

Related Publications (1)

• 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.

  PMID: 37802042 BACKGROUND

Related Links

• CHARM consortium website

Biospecimen

Retention: SAMPLES WITH DNA

Blood plasma and buffy coat samples, and/or DNA extracted from blood plasma and buffy coat samples.

MeSH Terms

Conditions

Neoplastic Syndromes, Hereditary; Colorectal Neoplasms, Hereditary Nonpolyposis; Hereditary Breast and Ovarian Cancer Syndrome; Stomach Neoplasms; Li-Fraumeni Syndrome

Condition Hierarchy (Ancestors)

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

Study Officials

• Raymond Kim, MD

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julia Sobotka, MSc

CONTACT

416-409-1387; charm@uhn.ca

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2024
• First Posted: December 10, 2024
• Study Start: April 19, 2024
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2031
• Last Updated: December 16, 2025

Record last verified: 2025-12

Locations

CA (8)