Increasing Uptake of Cascade Testing in Families With Familial Cancer Syndromes: A Randomized Controlled Trial of a Registry-aided Model.

May 29, 2026 updated by: National Cancer Centre, Singapore
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
545

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Singapore
      • Singapore, Singapore, 168583
        • National Cancer Centre, Singapore

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

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:

  • ARRs of a proband
  • Aged 21 years old and over
  • Singapore citizen or permanent resident

Exclusion Criteria:

  • Lacks capacity to consent
  • Not living in Singapore
  • Probands who decline to share relatives' contact details
  • Probands with no contactable relatives in Singapore

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Control arm: Proband-dependent approach
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.
Other: Proband-dependent approach
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.
Other Names:
  • Traditional approach; current standard of care
Experimental: Proband-dependent with registry-reminders approach
A registry-aided outreach to family members of probands to bypass the barriers inherent with the proband-dependent approach.
Other: Combination of the proband-dependent approach with additional registry-aided testing reminders

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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Up to 6 months after proband randomisation.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Barriers to cascade testing.
Time Frame: Through study completion, estimated up to 6 months.
Qualitative themes from interviews with relatives who decline testing.
Through study completion, estimated up to 6 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Cancer Centre, Singapore

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Clin Asst Prof Chiang Jianbang, MBBS, MRCP (UK), MMed, National Cancer Centre, Singapore

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 10, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 6, 2026

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 6, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 19, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 29, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 4, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 4, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 29, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 202104-00097

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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