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

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

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.

Study Overview

• Status: Recruiting
• Conditions: BRCA1 Mutation; BRCA2 Mutation; APC Gene Mutation; MLH1 Gene Mutation; RAD51C Gene Mutation; RAD51D Gene Mutation; BRIP1 Gene Mutation; PALB2 Gene Mutation; PTEN Gene Mutation; ATM Gene Mutation; CHEK2 Gene Mutation; BARD1 Gene Mutation; MSH2 Gene Mutation; MSH6 Gene Mutation; PMS2 Gene Mutation; POLD1 Gene Mutation; CDKN2A Mutation; POLE Gene Mutation; EPCAM Gene Mutation; BMPR1A Gene Mutation; SMAD4; GREM1
• Intervention / Treatment: Behavioral: Intervention Arm At-risk Relative/ARR Contacts; Behavioral: Standard of Care; Behavioral: MyGene Portal

• Study Type: Interventional
• Enrollment (Estimated): 2590
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kenneth Offit, MD, MPH; Phone Number: 646-888-4059; Email: offitk@mskcc.org
• Study Contact Backup: Name: Zsofia Stadler, MD; Phone Number: 646-888-4039; Email: stadlerz@mskcc.org

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
      • Contact: Kenneth Offit, MD, MPH; Phone Number: 646-888-4059
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
      • Contact: Kenneth Offit, MD, MPH; Phone Number: 646-888-4059
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (Limited Protocol Activity)
      • Contact: Kenneth Offit, MD, MPH; Phone Number: 646-888-4059
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)
      • Contact: Kenneth Offit, MD, MPH; Phone Number: 646-888-4059
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (Limited Protocol Activities)
      • Contact: Kenneth Offit, MD, MPH; Phone Number: 646-888-4059
    • New York, New York, United States, 10021
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Kenneth Offit, MD, MPH; Phone Number: 646-888-4059
    • New York, New York, United States, 10035
      • Recruiting
      • MSK at Ralph Lauren (Limited Protocol Activities)
      • Contact: Kenneth Offit, MD, MPH; Phone Number: 646-888-4059
    • Uniondale, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (Limited Protocol Activity)
      • Contact: Kenneth Offit, MD, MPH; Phone Number: 646-888-4059

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Study Population

Eligible probands will be identified through medical record review, CGS clinic schedule review, and internal CGS clinical patient logs. The study will be introduced to participants either during their genetic counseling session or through a follow-up email/phone call/MyMSK portal message/mail/text from the research study staff.

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Proband-Mediated Cascade Genetic Testing; 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.	Behavioral: Standard of Care; Participants will received appropriate clinical care as outline by standard of care guidelines
Experimental: EfFORT Trial Intervention Arm: Provider-Facilitated Cascade Genetic Testing; 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.	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.
Active Comparator: STRIVE Trial Control Arm: Patient-Led VUS Follow-Up; 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	Behavioral: Standard of Care; Participants will received appropriate clinical care as outline by standard of care guidelines
Experimental: STRIVE Trial Intervention Arm: Digitally-Facilitated VUS Follow-Up; 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.	Behavioral: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 α=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

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Kenneth Offit, MD, MPH, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: June 6, 2022
• First Submitted That Met QC Criteria: June 14, 2022
• First Posted (Actual): June 15, 2022

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Memorial Sloan Kettering Cancer Center; Genetic Testing; EfFORT; 22-023
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Genetic Diseases, Inborn; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Neoplastic Syndromes, Hereditary; Adenomatous Polyps; Adenoma; Intestinal Polyposis; Adenomatous Polyposis Coli
• Other Study ID Numbers: 22-023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No