Clinical trial NCT06726642: CfDNA in Hereditary And High-risk Malignancies 2
Official title: CfDNA in Hereditary And High-risk Malignancies (CHARM) 2: Evaluating the Performance of a cfDNA Blood Test for Early Cancer Detection
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: British Columbia Cancer Agency
name: Eastern Health
name: IWK Health Centre
name: Jewish General Hospital
name: Sinai Health System
name: The Hospital for Sick Children
First posted: 2024-12-10
Enrollment: 1000
Sex: ALL
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Determine the cancer detection rate of the cfDNA sequencing assay in patients with HCS.
timeFrame: 4 years from enrollment in the study.
Secondary outcomes:
measure: To assess the time to cancer diagnosis using cfDNA sequencing compared to controls.
timeFrame: 4 years from enrollment in the study.
measure: To assess the detection rate of cancers with no standard-of-care screening available using cfDNA sequencing.
timeFrame: 4 years from enrollment in the study.
measure: Assess the impact of tri-annual cfDNA testing on participant cancer worry.
timeFrame: 4 years from enrollment in the study.
measure: Assess the impact of tri-annual cfDNA testing on cancer risk perception.
timeFrame: 4 years from enrollment in the study.
measure: Assess the impact of tri-annual cfDNA testing on cancer anxiety and depression.
timeFrame: 4 years from enrollment in the study.
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: BC Cancer Agency
state: British Columbia
city: St. John's
country: Canada
facility: Eastern Health
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Toronto
country: Canada
facility: Sinai Health System
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Toronto
country: Canada
facility: Women's College Hospital
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Raymond Kim, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.