Genetic Testing Intervention for Cancer Risk

Recruiting at 7 trial locations

Overseen By Kenneth Offit, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: No email, No consent, Others

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

Compensation: Varies

Number of Visits: Unknown

2060 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to examine the impact of new cancer genetic counseling models that aim to increase patient engagement with the genetics team. To do this, the study consists of two trials to evaluate two related interventions. The first trial is the EfFORT Trial, which evaluates a cascade genetic testing intervention. Cascade testing is the process of offering genetic testing to people who are at risk of having inherited a possibly harmful gene change that has been found in their family. The study will look at how often genetic testing occurs when healthcare providers have permission to reach out to family members to recommend genetic testing and to help those who are interested get tested. The study will look at whether this cascade testing intervention is practical and effective. The study would like to see how this approach of healthcare providers reaching out directly to family members compares with the usual approach of patients telling their family members about the recommendation to get genetic testing. The second trial is the STRIVE Trial, which evaluates an intervention designed to help patients who receive an uncertain result from genetic testing (also called a "variant of uncertain significance") stay connected with their genetics care team, and to help patients and their primary care providers stay up-to-date about the meaning of uncertain genetic test results. The study will look at whether an intervention that consists of a study online portal for patients with uncertain genetic test results and their primary care providers will help them to stay up-to-date on the meaning of uncertain genetic test results. The study would like to see how this intervention compares to the usual approach of encouraging patients to re-contact their genetics care team on their own about a year after getting genetic testing."

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your healthcare provider.

What data supports the effectiveness of the treatment Intervention Arm At-risk Relative/ARR Contacts for cancer risk?

Research shows that interventions designed to help families communicate genetic testing results can improve the rate of relatives undergoing genetic testing for cancer risk. Specifically, these interventions have been effective in increasing cascade genetic testing for hereditary breast and ovarian cancer and Lynch syndrome, which can lead to better cancer prevention and early detection. ^{1 2 3 4 5}

Is genetic testing for cancer risk safe for humans?

The research on genetic testing for cancer risk, including methods like cascade testing, suggests it is generally safe for humans. These studies focus on the process of notifying and testing at-risk relatives, and while they don't specifically address safety concerns, they imply that the testing itself is not harmful. ^{4 5 6 7 8}

How does the Genetic Testing Intervention for Cancer Risk treatment differ from other treatments?

This treatment is unique because it focuses on improving family communication about genetic risks, encouraging relatives to undergo genetic testing, and facilitating 'cascade' testing, which is not typically emphasized in standard cancer treatments. It uses tools like online platforms and direct counselor contact to enhance outreach and communication, which are novel approaches compared to traditional methods. ^{1 2 5 9 10}

Research Team

Kenneth Offit, MD, MPH

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 25 who are patients at MSK, have recently received genetic counseling there, and understand English. They must have a relative also eligible to join. It's for those with certain gene mutations linked to cancer risk or relatives of such individuals. People can't join if they're unable or unwilling to consent, use the MyMSK patient portal, or don't have an email address.

Inclusion Criteria

Self-reported comprehension of written and verbal English language

Has at least one ARR who meets criteria for study enrollment (see below)

Current MSK patient

Exclusion Criteria

Is unwilling or unable to create a MyMSK patient portal account (see section 3.0 on MyMSK patient usage at MSK and CGS)

Is unwilling or unable to provide informed consent

I do not have an email address.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

EfFORT Trial Intervention

Provider-facilitated cascade genetic testing through telegenetics pre- and post-test counseling and saliva-based at-home testing

12 months

Ongoing virtual engagement

STRIVE Trial Intervention

Digitally-facilitated VUS follow-up with access to MyGene Portal for continuous engagement and updates

12 months

Ongoing virtual engagement

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Intervention Arm At-risk Relative/ARR Contacts

Trial Overview The study tests a 'cascade' approach where healthcare providers contact family members directly about genetic testing for inherited cancer risks versus the usual method of patients informing their relatives themselves.

Participant Groups

Group I: STRIVE Trial Intervention Arm: Digitally-Facilitated VUS Follow-Up Experimental Treatment 1 Intervention

Following standard of care post-test genetic counseling, patients will be provided access to the MyGene Portal. Through this portal, participants will be able to continuously engage with interactive educational materials including information about Variant of uncertain significance/VUS results and recommendations, access tools for participants to communicate with the CGS team, access the interactive pedigree (FamGenix) to provide updates about personal/family medical history, receive notifications about VUS reclassification, and receive reminders to self-schedule a follow-up clinical visit to discuss updates. In this way, participants will have a transparent, ongoing, and structured follow-up plan for their VUS management.

Group II: EfFORT Trial Intervention Arm: Provider-Facilitated Cascade Genetic Testing Experimental Treatment 1 Intervention

Intervention arm-: Behavioral: Probands will give contact info for their ARR in the eDGP and indicate a date by which they will discuss the familial pathogenic variant with their ARR (can request a delay/halt to outreach). After this date the team will contact the ARR to invite them to review education and e-consent to the study. The study team will facilitate ARR cascade testing through telegenetics pre- and post-test counseling and saliva-based at home testing through MSK or a reference laboratory.

Group III: STRIVE Trial Control Arm: Patient-Led VUS Follow-Up Active Control 1 Intervention

Patients will receive standard of care post-test genetic counseling and discussion of implications for relatives, if any. Consistent with standard practice, most patients will likely be recommended against telling their relatives to seek genetic testing for the Variant of uncertain significance/VUS because it is not clinically useful. All participants with a VUS will be recommended to re-contact the MSK CGS in 1-2 years for updated information related to the VUS result

Group IV: EfFORT Trial De-Identified Non-Randomized Control Arm Active Control 1 Intervention

This control arm is comparable to true standard of care.

Group V: Proband-Mediated Cascade Genetic Testing Active Control 2 Interventions

Control arm- Behavioral: As per standard of care, probands will be given a Family Letter by their genetic counselor that they will be instructed to share with their at-risk relatives (ARR). In addition to the recommendation that ARR undergo genetic counseling and a list of local genetics clinics, this letter will include a link to the eDGP through which control ARR can enroll onto the present study. For these ARR, the eDGP will only be used to obtain study e-consent and to administer study surveys.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

Interventions aimed at facilitating family communication about genetic testing results for Hereditary Breast and Ovarian Cancer (HBOC) and Lynch Syndrome (LS) showed a small but significant improvement in cascade genetic testing rates, with an effect size of 0.169 (p = 0.014).

Despite the interventions including psychoeducational components and communication skills training, the overall effect on family communication was small and not statistically significant (g = 0.085, p = 0.344), indicating that while cascade testing improved, family communication strategies may need further refinement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interventions Facilitating Family Communication of Genetic Testing Results and Cascade Screening in Hereditary Breast/Ovarian Cancer or Lynch Syndrome: A Systematic Review and Meta-Analysis. Baroutsou, V., Underhill-Blazey, ML., Appenzeller-Herzog, C., et al.[2021]

Proband-mediated interventions in genetics clinics can significantly increase the percentage of at-risk relatives informed about their inherited cancer risk, with rates ranging from 54.0% to 95.5%.

These interventions, which include tailored genetic counseling and follow-up methods, may also lead to a higher likelihood of relatives contacting genetics clinics and pursuing genetic testing, although the evidence is not yet conclusive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proband-mediated interventions to increase disclosure of genetic risk in families with a BRCA or Lynch syndrome condition: a systematic review. Young, AL., Imran, A., Spoelma, MJ., et al.[2023]

In a meta-analysis of 87 studies, it was found that only 48% of relatives underwent cascade genetic counseling and 41% underwent genetic testing for hereditary cancer, highlighting a significant gap in the uptake of these potentially life-saving interventions.

Direct contact by medical teams with relatives resulted in a much higher uptake of genetic counseling (63% vs. 35%) and genetic testing for first-degree relatives (62% vs. 40%) compared to the traditional patient-mediated approach, suggesting that changing the method of communication could improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cascade Testing for Hereditary Cancer Syndromes: Should We Move Toward Direct Relative Contact? A Systematic Review and Meta-Analysis. Frey, MK., Ahsan, MD., Bergeron, H., et al.[2023]

The IMPACT study aims to improve cancer prevention and early detection by enhancing family communication of genetic test results and engagement with cancer risk management among individuals with inherited cancer predisposition, involving a diverse group of participants with pathogenic variants.

The study will evaluate the effectiveness of two interventions: a website to facilitate family communication and a digital tool to clarify genetic test results and management guidelines, with outcomes measured at 1, 3, and 12 months to assess improvements in communication and adherence to cancer risk management without causing overtreatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IMProving care After inherited Cancer Testing (IMPACT) study: protocol of a randomized trial evaluating the efficacy of two interventions designed to improve cancer risk management and family communication of genetic test results. Cragun, D., Beckstead, J., Farmer, M., et al.[2023]

The FamilyCONNECT tool was developed to help patients with Lynch Syndrome (LS) communicate genetic risk information to at-risk relatives, and it received positive feedback from 79% of survey respondents, indicating its potential effectiveness.

Key barriers to using FamilyCONNECT identified by genetics professionals included concerns about privacy and confidentiality (83%) and a lack of institutional resources (76%), suggesting that addressing these issues is crucial for successful implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and evaluation of an online, patient-driven, family outreach intervention to facilitate sharing of genetic risk information in families with Lynch syndrome. Pande, M., Peterson, S., Lynch, PM.[2022]

A new health system-led approach for notifying at-risk relatives about genetic testing for hereditary cancer risks has been developed, aiming to improve the reach and effectiveness of cascade screening.

This feasibility study will assess how well this notification process works, focusing on its acceptability and initial effectiveness, with the goal of informing future larger trials to enhance genetic risk communication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility, acceptability, and limited efficacy of health system-led familial risk notification: protocol for a mixed-methods evaluation. Blasi, PR., Scrol, A., Anderson, ML., et al.[2022]

An online initiative for cascade testing allowed 1101 carriers of cancer-associated genes to invite 2280 first-degree relatives for low-cost genetic testing, with a participation rate of 47.5%.

The program revealed that 4.9% of tested relatives had a pathogenic variant in a different gene, indicating that cascade testing can uncover additional genetic risks beyond the known familial variant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cascade Genetic Testing of Relatives for Hereditary Cancer Risk: Results of an Online Initiative. Caswell-Jin, JL., Zimmer, AD., Stedden, W., et al.[2020]

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]

In the Bahamas, 23% of unselected breast cancer patients carry BRCA1 or BRCA2 mutations, highlighting the importance of genetic testing for their relatives to access preventive measures like oophorectomy.

Direct communication by genetic counselors significantly increases the likelihood of relatives attending genetic testing appointments, with an 84% attendance rate compared to only 9% when contacted through the mutation carriers themselves.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for recruitment of relatives of BRCA mutation carriers to a genetic testing program in the Bahamas. Trottier, M., Lunn, J., Butler, R., et al.[2017]

The 'Your Family Connects' intervention was developed to improve communication about genetic risks for ovarian cancer among survivors and their relatives, utilizing insights from 14 citizen scientists and data from 261 surveys and 39 interviews.

The intervention offers a flexible contact menu for survivors to reach out to at-risk relatives, considering relationship dynamics and preferences, which may enhance the effectiveness of genetic counseling outreach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Your Family Connects: A Theory-Based Intervention to Encourage Communication About Possible Inherited Cancer Risk among Ovarian Cancer Survivors and Close Relatives. Zhao, J., McBride, CM., Campbell, GP., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Interventions Facilitating Family Communication of Genetic Testing Results and Cascade Screening in Hereditary Breast/Ovarian Cancer or Lynch Syndrome: A Systematic Review and Meta-Analysis. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Proband-mediated interventions to increase disclosure of genetic risk in families with a BRCA or Lynch syndrome condition: a systematic review. [2023]

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

Cascade Testing for Hereditary Cancer Syndromes: Should We Move Toward Direct Relative Contact? A Systematic Review and Meta-Analysis. [2023]

4. England pubmed.ncbi.nlm.nih.gov

IMProving care After inherited Cancer Testing (IMPACT) study: protocol of a randomized trial evaluating the efficacy of two interventions designed to improve cancer risk management and family communication of genetic test results. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Development and evaluation of an online, patient-driven, family outreach intervention to facilitate sharing of genetic risk information in families with Lynch syndrome. [2022]

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

Feasibility, acceptability, and limited efficacy of health system-led familial risk notification: protocol for a mixed-methods evaluation. [2022]

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

Cascade Genetic Testing of Relatives for Hereditary Cancer Risk: Results of an Online Initiative. [2020]

8. England pubmed.ncbi.nlm.nih.gov

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

9. Denmark pubmed.ncbi.nlm.nih.gov

Strategies for recruitment of relatives of BRCA mutation carriers to a genetic testing program in the Bahamas. [2017]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Your Family Connects: A Theory-Based Intervention to Encourage Communication About Possible Inherited Cancer Risk among Ovarian Cancer Survivors and Close Relatives. [2023]