Hereditary Cancer SyndromesNCT07626814
Increasing Uptake of Cascade Testing in Families With Familial Cancer Syndromes: A Randomized Controlled Trial of a Registry-aided Model.
A study testing Proband-dependent approach and Combination of the proband-dependent approach with additional registry-aided testing reminders in people with Hereditary Cancer Syndromes, run by National Cancer Centre, Singapore at 1 site in Singapore.
Trial summary
The purpose of this study is to compare the uptake rates of a patient-initiated model of cascade testing with a registry-aided model amongst relatives of patients identified to have a particular cancer predisposition gene. Read more about this study
- Who is it for?
- Ages 21 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Hereditary Cancer Syndromes
- What is being tested?
- Proband-dependent approach and Combination of the proband-dependent approach with additional registry-aided testing reminders
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 545 participants
- Where
- 1 siteSingapore
- Study dates
- 10 Dec 2021to 6 Feb 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 21 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Probands:
- Patients who undergo clinical genetic testing and seen at the Cancer Genetics Service (CGS) in National Cancer Centre Singapore
- Pathogenic variant/ likely pathogenic variant (PV/LPV) identified in a cancer predisposition gene
- Aged 21 years old and over
- Singapore citizen or permanent resident
- ARRs:
Show all 9Show fewer
- ARRs of a proband
- Aged 21 years old and over
- Singapore citizen or permanent resident
Who cannot join
- Lacks capacity to consent
- Not living in Singapore
- Probands who decline to share relatives' contact details
- Probands with no contactable relatives in Singapore
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to compare the uptake rates of a patient-initiated model of cascade testing with a registry-aided model amongst relatives of patients identified to have a particular cancer predisposition gene. Cascade testing allows the benefits of genetic testing to spread beyond the patient and enables other family members to make an informed choice on genetic testing. The researcher team hopes to study the rates of cascade testing using the two models, while concurrently comparing the adherence of identified carriers to risk management recommendations, including surveillance imaging and/or prophylactic surgeries. The team also aims to understand the willingness, acceptability and barriers of a registry-aided model.
Read the detailed description
Germline pathogenic/ likely pathogenic variants (PV/LPV) in cancer predisposition genes are defined as genetic alterations that increases an individual's susceptibility to cancer development. They are present in germ cells (egg or sperm) and can be passed down to subsequent generations.
Following the identification of a germline PV/LPV in a cancer predisposition gene in an index case presenting with disease (symptomatic proband), systematic cascade testing can be performed in relatives who have not yet developed disease (asymptomatic) to determine their future risk. Identifying asymptomatic carriers in families provides opportunities to ascertain hereditary risk, prevent disease via risk reduction surgery, diagnose disease in earlier stages, and ultimately improve clinical outcomes.
In spite of the evidence in support of cascade testing, there remain significant barriers to uptake that hinder the ability of a proband in Singapore to disseminate this critical information to his/her family.
The conventional approach to cascade testing in Singapore and most countries is to encourage probands with PV/LPV in cancer predisposition genes to relay this genetic information to their relatives and encourage them to see a genetic counsellor for discussion on predictive genetic testing. This proband-initiated disclosure is often suboptimal due to a myriad of reasons.
To improve the uptake rate of cascade testing in families at high risk of cancers, we propose a registry-aided outreach to family members of probands to bypass the barriers inherent with the proband-dependent approach. Our study shares the burden of communicating genetic results by having a healthcare professional reach out to family members and discuss the implications of germline cascade testing with at-risk relatives (ARRs). Alternative communication channels to reach out to relatives, independent of the proband, is thus created and propagated. This new model to enhance cascade testing features a two-pronged approach - personal communication by the proband, as well as a secondary registry-aided outreach to contact at-risk relatives.
This proposal is evaluated using a cluster randomized controlled trial to compare the effectiveness of the outreach program by comparing the cascade testing uptake rates between the current proband-dependent approach (control arm) and the combination of the proband-dependent approach with additional registry-aided testing reminders (experimental arm).
An in-depth interview with relatives who declined cascade testing will also be conducted to elucidate other barriers to cascade testing in the local population.
- Conditions
- Hereditary Cancer Syndromes
- Being tested
- Proband-dependent approach, Combination of the proband-dependent approach with additional registry-aided testing reminders
- Keywords
- Cascade genetic testing, Familial cancer syndromes, Genetic counselling, Cancer genetics, Registry-based intervention, Precision medicine, Preventive genomics, Genetic testing uptake, Randomized controlled trial, Population health
- Medical subject headings
- Neoplastic Syndromes, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Proband-dependent approachOther
Also called Traditional approach; current standard of care
Probands assigned to the control arm will be offered family letters to distribute to their at-risk relatives (ARRs). These family letters encourage relatives to see a general practitioner for a referral to genetic counselling and cascade testing.
Combination of the proband-dependent approach with additional registry-aided testing remindersOther
Like the control arm, probands will be given the same family letters to distribute to their ARRs. In addition, a genetics coordinator will contact their first-degree relatives (FDRs) by phone/ email to inform them about genetic testing and advise them to obtain a referral from a general practitioner. The coordinator will remind relatives of their eligibility for genetic testing and assist them with queries at 1, 3, and 6 months after initial contact.
Upon visiting for pre-test genetic counselling, FDRs will be further invited to provide contact details of other untested.
| Study group | Role | What they receive |
|---|---|---|
| Control arm: Proband-dependent approach | Other | The conventional approach to cascade testing whereby probands are advised to relay their genetic information to relatives and encourage them to see a genetic counsellor for discussion on predictive genetic testing. Family letters are given to probands to help disseminate this information. Receives: Other: Proband-dependent approach |
| Proband-dependent with registry-reminders approach | Experimental | A registry-aided outreach to family members of probands to bypass the barriers inherent with the proband-dependent approach. Receives: Other: Combination of the proband-dependent approach with additional registry-aided testing reminders |
What is being measured
The primary outcome is the main question the study is designed to answer.
Uptake of cascade genetic testing.
Proportion of at-risk FDRs who attend pre-test counselling and undergo cascade testing.
Measured: Up to 6 months after proband randomisation.
Secondary outcomes (1)
Barriers to cascade testing.
Qualitative themes from interviews with relatives who decline testing.
Measured: Through study completion, estimated up to 6 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2026
- Study start10 Dec 2021
- Primary completion6 Feb 2026
- Study completion6 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary Cancer SyndromesStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 545 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Centre, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Clin Asst Prof Chiang Jianbang, MBBS, MRCP (UK), MMed, Principal investigator, National Cancer Centre, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07626814
- Sponsor's protocol ID
- 202104-00097
- Status last verified
- May 2026
- First submitted
- 19 May 2026
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Increasing Uptake of Cascade Testing in Families With Familial Cancer Syndromes: A Randomized Controlled Trial of a Registry-aided Model.
- ClinicalTrials.gov ID
- NCT07626814
- Acronym / sponsor ID
- 202104-00097
- Conditions
- Hereditary Cancer Syndromes
- Keywords
- Cascade genetic testing, Familial cancer syndromes, Genetic counselling, Cancer genetics, Registry-based intervention, Precision medicine, Preventive genomics, Genetic testing uptake
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 545 participants (actual)
- Lead sponsor
- National Cancer Centre, SingaporeUniversity, hospital or other
- Study start
- 10 Dec 2021 (actual)
- Primary completion
- 6 Feb 2026 (actual)
- Study completion
- 6 Feb 2026 (actual)
- First posted
- 4 Jun 2026 (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 purpose of this study is to compare the uptake rates of a patient-initiated model of cascade testing with a registry-aided model amongst relatives of patients identified to have a particular cancer predisposition gene. Cascade testing allows the benefits of genetic testing to spread beyond the patient and enables other family members to make an informed choice on genetic testing. The researcher team hopes to study the rates of cascade testing using the two models, while concurrently comparing the adherence of identified carriers to risk management recommendations, including surveillance imaging and/or prophylactic surgeries. The team also aims to understand the willingness, acceptability and barriers of a registry-aided model.
Detailed description
Germline pathogenic/ likely pathogenic variants (PV/LPV) in cancer predisposition genes are defined as genetic alterations that increases an individual's susceptibility to cancer development. They are present in germ cells (egg or sperm) and can be passed down to subsequent generations.
Following the identification of a germline PV/LPV in a cancer predisposition gene in an index case presenting with disease (symptomatic proband), systematic cascade testing can be performed in relatives who have not yet developed disease (asymptomatic) to determine their future risk. Identifying asymptomatic carriers in families provides opportunities to ascertain hereditary risk, prevent disease via risk reduction surgery, diagnose disease in earlier stages, and ultimately improve clinical outcomes.
In spite of the evidence in support of cascade testing, there remain significant barriers to uptake that hinder the ability of a proband in Singapore to disseminate this critical information to his/her family.
The conventional approach to cascade testing in Singapore and most countries is to encourage probands with PV/LPV in cancer predisposition genes to relay this genetic information to their relatives and encourage them to see a genetic counsellor for discussion on predictive genetic testing. This proband-initiated disclosure is often suboptimal due to a myriad of reasons.
To improve the uptake rate of cascade testing in families at high risk of cancers, we propose a registry-aided outreach to family members of probands to bypass the barriers inherent with the proband-dependent approach. Our study shares the burden of communicating genetic results by having a healthcare professional reach out to family members and discuss the implications of germline cascade testing with at-risk relatives (ARRs). Alternative communication channels to reach out to relatives, independent of the proband, is thus created and propagated. This new model to enhance cascade testing features a two-pronged approach - personal communication by the proband, as well as a secondary registry-aided outreach to contact at-risk relatives.
This proposal is evaluated using a cluster randomized controlled trial to compare the effectiveness of the outreach program by comparing the cascade testing uptake rates between the current proband-dependent approach (control arm) and the combination of the proband-dependent approach with additional registry-aided testing reminders (experimental arm).
An in-depth interview with relatives who declined cascade testing will also be conducted to elucidate other barriers to cascade testing in the local population.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control arm: Proband-dependent approach | Other | Other: Proband-dependent approachThe conventional approach to cascade testing whereby probands are advised to relay their genetic information to relatives and encourage them to see a genetic counsellor for discussion on predictive genetic testing. Family letters are given to probands to help disseminate this information. |
| Proband-dependent with registry-reminders approach | Experimental | Other: Combination of the proband-dependent approach with additional registry-aided testing remindersA registry-aided outreach to family members of probands to bypass the barriers inherent with the proband-dependent approach. |
Who may qualify
- Ages
- 21 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients who undergo clinical genetic testing and seen at the Cancer Genetics Service (CGS) in National Cancer Centre Singapore
- Pathogenic variant/ likely pathogenic variant (PV/LPV) identified in a cancer predisposition gene
- Aged 21 years old and over
- Singapore citizen or permanent resident
- ARRs of a proband
Key exclusion criteria (4 listed)
- Lacks capacity to consent
- Not living in Singapore
- Probands who decline to share relatives' contact details
- Probands with no contactable relatives in Singapore
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 |
|---|---|---|
| Proband-dependent approachAlso: Traditional approach; current standard of careProbands assigned to the control arm will be offered family letters to distribute to their at-risk relatives (ARRs). These family letters encourage relatives to see a general practitioner for a referral to genetic counselling and cascade testing. | Other | Control arm: Proband-dependent approach |
| Combination of the proband-dependent approach with additional registry-aided testing remindersLike the control arm, probands will be given the same family letters to distribute to their ARRs. In addition, a genetics coordinator will contact their first-degree relatives (FDRs) by phone/ email to inform them about genetic testing and advise them to obtain a referral from a general practitioner. The coordinator will remind relatives of their eligibility for genetic testing and assist them with queries at 1, 3, and 6 months after initial contact. Upon visiting for pre-test genetic counselling, FDRs will be further invited to provide contact details of other untested. | Other | Proband-dependent with registry-reminders approach |
Primary outcome
Uptake of cascade genetic testing.
Time frame: Up to 6 months after proband randomisation.
Proportion of at-risk FDRs who attend pre-test counselling and undergo cascade testing.
1 secondary outcome
Barriers to cascade testing.
Time frame: Through study completion, estimated up to 6 months.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Clin Asst Prof Chiang Jianbang, MBBS, MRCP (UK), MMed principal investigator
National Cancer Centre, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Proband-dependent approach and Combination of the proband-dependent approach with additional registry-aided testing reminders in people with Hereditary Cancer Syndromes, run by National Cancer Centre, Singapore at 1 site in Singapore.
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 9 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: finished, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Uptake of cascade genetic testing. (time frame: Up to 6 months after proband randomisation.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Jun 2026.