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

260 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Enhanced cascade testing for cancer?

Research shows that cascade genetic testing helps identify at-risk relatives of patients with hereditary cancer syndromes, allowing them to pursue cancer screening and prevention strategies, which can reduce cancer-related illness and death. Studies also highlight that improving access to cascade testing through dedicated clinics and telephone counseling increases the uptake of this testing, making it more effective in preventing cancer. ^{1 2 3 4 5}

Is Enhanced Genetic Testing for Cancer safe for humans?

The research articles do not provide specific safety data for Enhanced Genetic Testing for Cancer, but they focus on the process of identifying at-risk relatives for genetic conditions, which is generally considered safe. ^{1 2 3 6 7}

How is the Enhanced cascade testing treatment different from other treatments for cancer?

Enhanced cascade testing is unique because it focuses on identifying at-risk relatives of patients with hereditary cancer syndromes through genetic testing, allowing for early cancer prevention strategies. Unlike traditional treatments that target existing cancer, this approach aims to prevent cancer by informing relatives about their genetic risks and encouraging proactive health measures. ^{1 2 3 6 8}

What is the purpose of this trial?

CHARGE is a hybrid type I feasibility study to compare a choice architecture intervention for cascade genetic testing to usual care.

Research Team

Sukh Makhnoon, PhD, MS

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Facilitated cascade testing (FaCT): a randomized controlled trial. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Cascade testing after exome sequencing: Retrospective analysis of linked family data at 2 US laboratories. [2023]

3. United States 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Implementation of a dedicated cascade testing clinic for patients at risk for hereditary cancer syndromes. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Prospective Feasibility Trial of a Novel Strategy of Facilitated Cascade Genetic Testing Using Telephone Counseling. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Implementation of cascade testing for the detection of familial hypercholesterolaemia. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Cascade testing for hereditary cancer: comprehensive multigene panels identify unexpected actionable findings in relatives. [2023]

8. Switzerland 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. [2023]