An Intervention to Increase Genetic Testing in Families Who May Share a Gene Mutation Related to Cancer Risk

BRCA1 Mutation Clinical Trial

Official title:

Digital Technology to Enhance Access to and Effectiveness of Cancer Genetic Counseling: Effective Familial OutReach Via Tele-genetics (EfFORT) Trial & Supporting Test Result Interpretation and Variant Education (STRIVE) Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05420064
• Other study ID #: 22-023
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2022
• Est. completion date: November 30, 2026

Study information

• Verified date: March 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Kenneth Offit, MD, MPH
• Phone: 646-888-4059
• Email: offitk[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate 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. This process is repeated as more people within the family are found to have the gene change. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2590
• Est. completion date: November 30, 2026
• Est. primary completion date: May 31, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years and older

Eligibility

Inclusion Criteria:

EfFORT Trial Probands

• Current MSK patient
• Received post-test genetic counseling from MSK Clinical Genetics Service within the last 3 months
• 25 years of age or older
• Self-reported "very well" comprehension of written and verbal English language
• Has at least one ARR who meets criteria for study enrollment (see below)
• First in the family to test positive for PV at MSK in any of the following cancer susceptibility genes, or an ARR of an MSK proband who converted to the proband role: APC I1307K GREM1 RAD51D ATM MLH1 SMAD4 BARD1 MSH2 BMPR1A MSH6 BRCA1 PALB2 BRCA2 PMS2 BRIP1 POLD1 CDKN2A (P16) POLE CHEK2 PTEN EPCAM RAD51C Principal Investigator discretion will be used to determine whether specific variants within the above genes meet a clinical actionability threshold to warrant familial genetic testing.

EfFORT Trial At-Risk Relatives (ARRs):

• Biological first-, second-, or third- degree relative of enrolled MSK proband
• 25 years of age or older
• Resides within the United States
• Self-reported medical insurance which can be in or out of network with MSK
• Self-reported "very well" comprehension of written and verbal English language STRIVE Trial VUS Patients
• Current MSK patient
• Received post-test genetic counseling from MSK Clinical Genetics Service within the last 3 months
• 25 years of age or older
• Self-reported "very well" comprehension of written and verbal English language
• Has a VUS identified in any of the following cancer predisposition genes:

APC CDK4 MAX MUTYH RAD51B SMAD4 ATM CDKN2A (P16) MBD4 NF1 RAD51C STK11 AXIN2 CHEK2 MEN1 NF2 RAD51D TERT BAP1 CTNNA1 MET NTHL1 RET TMEM127 BARD1 DICER1 MITF PALB2 RNF43 TP53 BLM EPCAM MITF PMS2 RPS20 TSC1 BMPR1A EPCAM MLH1 POLD1 SDHA TSC2 BRCA1 FH MLH3 POLE SDHAF2 VHL BRCA2 FLCN MSH2 POT1 SDHB BRIP1 GREM1 MSH3 PTCH1 SDHC CDH1 HOXB13 MSH6 PTEN SDHD

STRIVE Trial PCP Providers:

• Designated healthcare provider for an enrolled VUS patient
• Resides within the United States Exclusion Criteria: EfFORT Trial Probands
• Is unwilling or unable to provide informed consent
• Is unwilling or unable to create a MyMSK patient portal account (see section 3.0 on MyMSK patient usage at MSK and CGS)
• Does not have an email address
• Has enrolled in the STRIVE trial

EfFORT Trial At-Risk Relatives (ARRs):

• Is unwilling or unable to provide informed consent
• Is unwilling or unable to create a MyMSK patient portal account
• Has previously undergone genetic testing for the familial PV
• Does not have an email address
• Has opted out of study contact STRIVE Trial VUS Patients
• Is unwilling or unable to provide informed consent
• Is unwilling or unable to create a MyMSK patient portal account (see section 3.0 on MyMSK patient usage at MSK and CGS)
• Does not have an email address
• Has enrolled in the EfFORT trial STRIVE Trial PCP Providers
• Contact information not available

Related Conditions & MeSH terms

• Adenomatous Polyposis Coli
• ATM Gene Mutation
• BARD1 Gene Mutation
• BRCA1 Mutation
• BRCA2 Mutation
• BRIP1 Gene Mutation
• CHEK2 Gene Mutation
• MLH1 Gene Mutation
• MSH2 Gene Mutation
• MSH6 Gene Mutation
• PALB2 Gene Mutation
• PMS2 Gene Mutation
• POLD1 Gene Mutation
• POLE Gene Mutation
• PTEN Gene Mutation
• RAD51C Gene Mutation
• RAD51D Gene Mutation

Intervention

Behavioral:
• Intervention Arm At-risk Relative/ARR Contacts
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.
• MyGene Portal
Through the MyGene Portal, participants will be able to continually access their genetic test results, personalized medical management recommendations from the MSK CGS care team, an interactive pedigree for personal/family history updates, and tailored educational materials for patients with a VUS in an effort to promote sustained engagement and transparency.
• Standard of Care
Participants will received appropriate clinical care as outline by standard of care guidelines

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Limited Protocol Activity)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	MSK at Ralph Lauren (Limited Protocol Activities)	New York	New York
United States	Memorial Sloan Kettering Nassau (Limited Protocol Activity)	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of genetic testing uptake in provider-facilitated cascade testing intervention to the proband-mediated cascade testing control	The Primary Objective for EfFORT Trial: Assess genetic testing uptake by first-, second-, and third-degree relatives in the provider-facilitated cascade testing intervention as compared to the proband-mediated cascade testing control.	12 months
Primary	Comparison of participant perceived quality of care	The Primary Objective for STRIVE Trial: Assess perceived quality of Variant of uncertain significance/VUS follow-up care and continued engagement with the Clinical Genetics Service/CGS care team in the digitally-facilitated VUS follow-up intervention as compared to the patient-led VUS follow-up control. A modified subset of items based upon an existing survey of patient-centered quality of follow-up care for cancer survivors (Cronbach's a=0.65-0.93) will be used to measure patient perceptions of the quality of their follow-up care provided by both the CGS care team (11 items) and their PCPs (6 items). Items are measured on a 4-point Likert-type scale, and mean scores are computed such that higher scores indicate greater perceived quality of care This measure will be collected from VUS patient participants in both study arms and a mean score calculated across items.	12 months

External Links

•   Memorial Sloan Kettering Cancer Center