Hereditary Cancer SyndromeCHARM2NCT06726642
CfDNA in Hereditary And High-risk Malignancies 2
An observational study of Hereditary Cancer Syndrome, run by University Health Network, Toronto at 8 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 90 years
- Conditions the study is for
- Hereditary Cancer Syndrome
- What is being tested?
- Cell-free DNA analysis
- How many people
- 1,000 participants
- Where
- 8 sitesCanada
- Study dates
- 19 Apr 2024to Dec 2031
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 90 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
Canada8 sites, 8 recruiting
- Recruiting
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8
Lynette Penney, MD, 902-470-8754, lynette.penney@iwk.nshealth.ca
Lynette Penney, MD
- Recruiting
Jewish General Hospital
Montreal, Quebec, H3T 1E2
William Foulkes, MD, 514-934-1934 ext. Ext 44121, william.foulkes@mcgill.ca
Mark Basik, MD, mark.basik@mcgill.ca
- Recruiting
Newfoundland and Labrador Health Services (previously Eastern Health)
St. John's, Newfoundland and Labrador, A1B 3V6
Angela Hyde, 709-749-9686, Angela.Hyde@nlhealthservices.ca
Angela Hyde, MD
- Recruiting
The Hospital for Sick Children
Toronto, Ontario, M5G 1E8
David Malkin, 416-813-5348, david.malkin@sickkids.ca
David Malkin, MD
- Recruiting
Sinai Health System
Toronto, Ontario, M5G 1X5
Raymond Kim, MD, 416-586-4800 ext. Ext. 4220, raymond.kim@uhn.ca
Raymond Kim, MD
- Recruiting
University Health Network
Toronto, Ontario, M5G 2M9
Raymond Kim, MD, 416-586-4800 ext. Ext. 4220, raymond.kim@uhn.ca
Julia Sobotka, MSc, julia.sobotka@uhn.ca
- Not yet recruiting
Women's College Hospital
Toronto, Ontario, M5S 1B2
Gabby Ene, (416)-946-4501 ext. Ext. 3969, gabrielle.ene@uhnresearch.ca
Michelle Jacobson, MD
- Recruiting
BC Cancer Agency
Vancouver, British Columbia, V5Z 4E6
Intan Schrader, MD, 604-877-6000 ext. Ext. 672198, ischrader@bccancer.bc.ca
Sara Singh, sara.singh@bccancer.bc.ca
About this study
Official title: CfDNA in Hereditary And High-risk Malignancies (CHARM) 2: Evaluating the Performance of a cfDNA Blood Test for Early Cancer Detection
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.
Read the detailed description
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
- Hereditary Cancer Syndrome
- Being tested
- Cell-free DNA analysis
- 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
- Medical subject headings
- Neoplastic Syndromes, Hereditary, Colorectal Neoplasms, Hereditary Nonpolyposis, Hereditary Breast and Ovarian Cancer Syndrome, Stomach Neoplasms, Li-Fraumeni Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cell-free DNA analysisDiagnostic 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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 4 years from enrollment in the study.
Secondary outcomes (5)
To assess the time to cancer diagnosis using cfDNA sequencing compared to controls.
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.
Measured: 4 years from enrollment in the study.
To assess the detection rate of cancers with no standard-of-care screening available using cfDNA sequencing.
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).
Measured: 4 years from enrollment in the study.
Assess the impact of tri-annual cfDNA testing on participant cancer worry.
The investigators will assess the impact of tri-annual cfDNA testing on participants' cancer related worry, using the Cancer Worry Scale (PMID: 19382100).
Measured: 4 years from enrollment in the study.
Assess the impact of tri-annual cfDNA testing on cancer risk perception.
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).
Measured: 4 years from enrollment in the study.
Assess the impact of tri-annual cfDNA testing on cancer anxiety and depression.
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).
Measured: 4 years from enrollment in the study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2024
- Study start19 Apr 2024
- Primary completionDec 2029 (estimated)
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary Cancer SyndromeStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- British Columbia Cancer Agency, IWK Health Centre, Jewish General Hospital, Sinai Health System, The Hospital for Sick Children, University of Alberta, Women's College Hospital, Eastern Health
- Responsible party
- Sponsor
- Investigators
- Raymond Kim, MD, Principal investigator, Princess Margaret Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06726642
- Sponsor's protocol ID
- 23-5766
- Acronym
- CHARM2
- Status last verified
- Oct 2026
- First submitted
- 8 Nov 2024
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 37802042
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CfDNA in Hereditary And High-risk Malignancies (CHARM) 2: Evaluating the Performance of a cfDNA Blood Test for Early Cancer Detection
- ClinicalTrials.gov ID
- NCT06726642
- Acronym / sponsor ID
- CHARM2 / 23-5766
- Conditions
- Hereditary Cancer Syndrome
- Keywords
- cfDNA, cell-free DNA, Hereditary cancer syndrome, BRCA1, BRCA2, Lynch Syndrome, Hereditary breast and ovarian cancer (HBOC), Liquid biopsy
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- British Columbia Cancer Agency, IWK Health Centre, Jewish General Hospital, Sinai Health System, The Hospital for Sick Children, University of Alberta, Women's College Hospital, Eastern Health
- Study start
- 19 Apr 2024 (actual)
- Primary completion
- Dec 2029 (estimated)
- Study completion
- Dec 2031 (estimated)
- First posted
- 10 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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), 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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Test cohort | – | Diagnostic Test: Cell-free DNA analysisAll 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. |
| 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. |
Who may qualify
- Ages
- Up to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cell-free DNA analysisAnalysis 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). | Diagnostic test | Test cohort |
Primary outcome
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).
5 secondary outcomes
To assess the time to cancer diagnosis using cfDNA sequencing compared to controls.
Time frame: 4 years from enrollment in the study.
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.
Assess the impact of tri-annual cfDNA testing on participant cancer worry.
Time frame: 4 years from enrollment in the study.
Assess the impact of tri-annual cfDNA testing on cancer risk perception.
Time frame: 4 years from enrollment in the study.
Assess the impact of tri-annual cfDNA testing on cancer anxiety and depression.
Time frame: 4 years from enrollment in the study.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2026.
- Background: PubMed 37802042Farncombe 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.
- CHARM consortium websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Raymond Kim, MD principal investigator
Princess Margaret Cancer Centre
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hereditary Cancer Syndrome, run by University Health Network, Toronto at 8 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Julia Sobotka, MSc (416-409-1387, charm@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the cancer detection rate of the cfDNA sequencing assay in patients with HCS. (time frame: 4 years from enrollment in the study.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06726642, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026.