Enhanced Genetic Testing for Cancer

(CHARGE Trial)

Overseen By Sukh Makhnoon, PhD, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Referred by relative, Unwilling to randomize

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new method of offering genetic testing to family members, known as choice architecture, is more effective than the usual approach. It involves sending genetic testing kits directly to relatives of individuals with specific genetic changes linked to cancer, such as BRCA1 or BRCA2. The goal is to determine if this method simplifies and speeds up the testing process for families. Individuals with a newly identified genetic change in certain cancer-related genes and at least one adult relative in Texas might be suitable candidates. This method is called enhanced cascade testing. As an unphased trial, it provides participants the opportunity to contribute to innovative research that could simplify genetic testing for families.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that enhanced cascade testing is safe?

Research has shown that enhanced cascade testing for hereditary cancer is safe. This testing involves checking the family members of someone with a genetic condition. Studies indicate that this process helps people understand their risk without causing major side effects. Most participants in these studies found the testing easy to handle. No significant adverse health reactions have been linked to the testing. Overall, enhanced cascade testing is designed to be safe and helpful for families seeking to learn more about their health risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the enhanced cascade testing for cancer because it introduces a more direct and accessible method for genetic testing. Unlike the standard approach, which typically requires relatives to seek genetic counseling and testing on their own, the new method directly mails genetic testing kits to the relatives of individuals diagnosed with cancer. This approach could significantly increase participation in genetic testing, helping families understand their cancer risks more easily and quickly. By simplifying the process, there's potential for earlier detection and prevention strategies, making it a promising development in cancer care.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that testing family members for genetic risks effectively identifies cancer risks. It helps identify family members who might be unaware of their genetic risk for cancer. Studies indicate that when people know their risk, they can take steps like more frequent check-ups or lifestyle changes to maintain better health. In this trial, participants will be in one of two groups: one receiving standard of care cascade genetic testing, and another receiving genetic testing kits directly mailed to family members, known as choice architecture cascade testing. Early evidence suggests this direct mailing approach can help families make informed health decisions. ^{2 6 7 8 9}

Who Is on the Research Team?

Sukh Makhnoon, PhD, MS

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with cancer. Specific eligibility criteria are not provided, so it's important to contact the study team for more details on who can participate.

Inclusion Criteria

Relative: Residing in Texas

Proband: English fluency

Relative: English fluency

Exclusion Criteria

I am not willing to be randomly assigned to a study group.

I was recommended for genetic testing because a family member has a known genetic mutation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention

Participants receive either standard genetic counseling or a direct mailed genetic testing kit

3-6 months

Follow-up

Participants are monitored for satisfaction, family functioning, and communication about genetic test results

4-7 months

What Are the Treatments Tested in This Trial?

Interventions

• Enhanced cascade testing

Trial Overview The CHARGE study is testing a new approach called 'enhanced cascade testing' against the usual care given for genetic testing in cancer patients. It aims to see if this method improves the process and outcomes of genetic testing.

How Is the Trial Designed?

Group I: Choice architecture cascade testing Experimental Treatment 1 Intervention

Direct mailed genetic testing kit to probands' relatives.

Group II: Standard of care cascade testing Active Control 1 Intervention

Standard of care cascade genetic testing

Enhanced cascade testing is already approved in European Union, United States, Switzerland for the following indications:

Approved in European Union as Cascade Genetic Testing for:

• Hereditary Breast and Ovarian Cancer Syndrome (HBOC)
• Lynch Syndrome
• Familial Hypercholesterolemia (FH)

Approved in United States as Cascade Genetic Testing for:

• Hereditary Breast and Ovarian Cancer Syndrome (HBOC)
• Lynch Syndrome
• Familial Hypercholesterolemia (FH)
• Other hereditary cancer syndromes

Approved in Switzerland as Cascade Genetic Testing for:

• Hereditary Breast and Ovarian Cancer Syndrome (HBOC)
• Lynch Syndrome
• Familial Hypercholesterolemia (FH)

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

Cascade genetic testing for cancer risk in relatives of individuals with hereditary breast and ovarian cancer (HBOC) or Lynch syndrome is a valuable public health intervention, but its effectiveness varies based on the healthcare system and cultural context in countries like Switzerland, Korea, and Israel.

The implementation of cascade testing faces ethical, legal, and social implications (ELSI) that can hinder access to genetic services and affect the perceived value of the information gained, highlighting the tension between individual rights and public health interests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Privacy and utility of genetic testing in families with hereditary cancer syndromes living in three countries: the international cascade genetic screening experience. Barnoy, S., Dagan, E., Kim, S., et al.[2023]

Cascade testing for familial hypercholesterolaemia is shown to be cost-effective and increases the uptake of preventive measures, although its implementation is limited to a few countries due to funding and infrastructure challenges.

While statins have been effective in improving vascular function in children with familial hypercholesterolaemia, there is a lack of extensive safety data, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of cascade testing for the detection of familial hypercholesterolaemia. Hadfield, SG., Humphries, SE.[2022]

In a pilot study involving 95 at-risk relatives of patients with hereditary cancer syndromes, 76% participated in a 2-year follow-up, with 44% of those tested found to have inherited pathogenic variants, leading to targeted cancer prevention strategies.

The study showed that clinician-facilitated cascade genetic testing not only improved cancer screening rates (with 72% completing at least one recommended screening) but also maintained a good quality of life, as indicated by low levels of anxiety and distress among participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What happens in the long term: Uptake of cancer surveillance and prevention strategies among at-risk relatives with pathogenic variants detected via cascade testing. Frey, MK., Ahsan, MD., Badiner, N., et al.[2023]

In a study involving 3696 relatives of cancer patients, cascade testing with multigene panels revealed unexpected pathogenic variants in 6.2% of relatives, highlighting the importance of broader genetic testing beyond just familial variants.

36.3% of relatives with unexpected pathogenic variants would have qualified for different or additional cancer screening recommendations, suggesting that limiting testing to known familial variants could lead to missed opportunities for preventive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cascade testing for hereditary cancer: comprehensive multigene panels identify unexpected actionable findings in relatives. Heald, B., Pirzadeh-Miller, S., Ellsworth, RE., et al.[2023]

Only 7.6% of at-risk relatives completed cascade testing after a positive exome sequencing result from 3723 probands, indicating low uptake of this important follow-up testing.

Despite the low uptake, 47% of the relatives who were tested received clinically significant results, highlighting the potential value of cascade testing for informing clinical management and reproductive decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cascade testing after exome sequencing: Retrospective analysis of linked family data at 2 US laboratories. Stefka, J., Streff, H., Liu, P., et al.[2023]

The FaCT trial aims to determine if a facilitated cascade testing strategy can significantly increase the uptake of genetic testing among first-degree relatives of patients with BRCA1/2 mutations compared to standard care, which relies on probands to share information.

The study will involve 150 probands and is expected to include around 450 first-degree relatives, with results anticipated by January 2024, highlighting the potential for improved cancer prevention through better genetic testing access.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Facilitated cascade testing (FaCT): a randomized controlled trial. Nitecki, R., Moss, HA., Watson, CH., et al.[2022]

The implementation of a dedicated Cascade Testing Clinic (CTC) significantly reduced the average wait time for appointments from 144 days in the New Patient Clinic (NPC) to just 46 days, making genetic testing more accessible for at-risk relatives.

The CTC also improved patient attendance rates, with a no-show/cancellation rate of 11.7% compared to 29.7% in the NPC, and allowed genetic counselors to see nearly twice as many patients, enhancing overall clinic efficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of a dedicated cascade testing clinic for patients at risk for hereditary cancer syndromes. Jacobs, MF., Koeppe, ES., Chase, CL., et al.[2023]

Facilitated cascade testing, which included telephone counseling and mailed saliva kits, achieved a high uptake of genetic testing among at-risk relatives (ARRs), with 66 out of 114 identified ARRs completing the testing.

Among those who completed testing, 41% were found to carry the familial pathogenic variant, leading to proactive cancer surveillance and risk-reducing surgeries, demonstrating the potential of this approach to enhance early detection and reduce cancer mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Feasibility Trial of a Novel Strategy of Facilitated Cascade Genetic Testing Using Telephone Counseling. Frey, MK., Kahn, RM., Chapman-Davis, E., et al.[2021]

Citations

1. nature.com nature.com/articles/s41525-024-00412-0

Strategies to improve implementation of cascade testing in ... Cascade testing allows the benefits of genetic testing to propagate beyond the affected patients, and empower family members to understand their ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1098360023009966

Systematic evidence review and meta-analysis of ... We conducted a systematic review and meta-analysis of 17 patient-reported and health-services-related outcomes associated with pre- and post-test GC in GCRA.

3. hccpjournal.biomedcentral.com hccpjournal.biomedcentral.com/articles/10.1186/s13053-021-00198-7

Improving our model of cascade testing for hereditary cancer ... Consensus and evidence suggest that cascade testing is critical to achieve the promise of cancer genetic testing.

4. ascopubs.org ascopubs.org/doi/10.1200/GO-24-00387

Cascade Testing Among Patients With Breast Cancer Cascade testing offers several benefits, including the identification of at-risk individuals who can benefit from enhanced surveillance, risk- ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11751770/

Cascade genetic testing: an underutilized pathway to ... Cascade genetic testing represents a powerful application of precision medicine and involves the process of familial diffusion or the “cascade” of genomic risk ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9746789/

Cascade Testing for Hereditary Cancer Syndromes We sought to compare outcomes associated with patient-mediated and direct relative contact for hereditary cancer cascade genetic counseling and testing.

7. doh.wa.gov doh.wa.gov/you-and-your-family/genetic-services/individuals-families/cascade-screening

Cascade Screening | Washington State Department of Health Cascade screening helps find out if relatives of people diagnosed with genetic conditions might be at risk. Some genetic conditions run in families, passing ...

8. acog.org acog.org/clinical/clinical-guidance/committee-opinion/articles/2018/01/cascade-testing-testing-women-for-known-hereditary-genetic-mutations-associated-with-cancer

Cascade Testing: Testing Women for Known Hereditary ... Cascade testing refers to the performance of genetic counseling and testing in blood relatives of individuals who have been identified with specific genetic ...

9. academic.oup.com academic.oup.com/jnci/article/111/1/95/5099030

Cascade Genetic Testing of Relatives for Hereditary Cancer ... In cascade testing, genetic testing for an identified familial pathogenic variant extends to disease-free relatives to allow genetically ...