Reach and Engagement of GENetic Education, Risk Assessment, and TEsting Feasibility Trial (REGENERATE)

Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed at advanced stages and has poor survival. Approximately 10% of patients with PDAC have a pathogenic germline variant in a cancer gene, and national guidelines recommend genetic testing in patients with PDAC and their at-risk relatives. Surveillance in individuals at risk for PDAC has been associated with earlier-stage detection and improved survival. However, uptake of genetic testing among individuals at risk for hereditary cancer syndromes is often low, and this gap is especially pronounced in Black, Latino/a, and Medicaid-enrolled populations. This study is designed to address this gap by evaluating a lower-cost, patient-driven remote model for PDAC genetic education/testing and multi-cancer early detection (MCED) education/testing.

The REGENERATE Feasibility Trial is a randomized feasibility study evaluating a novel intervention consisting of phone-based navigation delivered through a trusted national pancreatic cancer organization, PanCAN, compared with routine online educational materials alone. The study will assess whether this approach can improve uptake of germline genetic testing and MCED testing among individuals at risk for PDAC who have obstacles to healthcare access. The trial specifically focuses on Black, Latino/a, and Medicaid-enrolled individuals at risk for PDAC who reside in Massachusetts, reflecting the study goal of improving access to cancer genetics and early detection services.

The study plans to randomize 80 individuals at risk for PDAC, approximately 40 per arm, and will enroll until 80 participants have been randomized. This is a single-site HCC study with collaborating partners assisting with study outreach. Participants must live in Massachusetts, speak English, have internet access, and be willing to travel to Dana-Farber Cancer Institute in Boston for diagnostic testing if an MCED result indicates possible malignancy. Eligible participants must be aged 50 years or older or within 10 years of the earliest PDAC diagnosis in the family, and must be currently enrolled in Medicaid and/or identify as Black and/or Latino/a, with no prior PDAC-related genetic testing.

After consent and completion of the baseline survey, participants will be randomized through REDCap to 1 of 2 study arms. In the online education arm, participants will receive links to the testing company's educational websites and review materials at their own pace. In the PanCAN telephone education arm, a trained PanCAN educator will conduct a scheduled telephone session. The telephone session includes approximately 10 minutes of education about pancreatic cancer, genetic risk, and genetic testing, followed during the same call by approximately 10 minutes of education about the risks, benefits, and limitations of MCED testing. After either the phone session or online review, participants complete a post-education survey assessing satisfaction, knowledge, and preparation for decision-making. Receipt of genetic testing and/or MCED testing is optional, and participants may take up to 3 months to opt in to testing if accrual remains open.

For participants who choose genetic testing, the study team will facilitate ordering through the testing company, which will mail a saliva kit to the participant's home. For participants who choose MCED testing, the testing company will arrange either home phlebotomy or blood collection at a local facility based on participant preference. Genetic and MCED results are returned directly to the study team. Negative results are generally communicated by email and mail. Positive genetic results trigger telephone follow-up from a Dana-Farber clinical genetic counselor for clinical navigation. Participants with a positive MCED result will be contacted for phone, virtual, or in-person follow-up with a Dana-Farber provider familiar with MCED testing and invited to Dana-Farber for diagnostic workup until resolution. Recommended workup may include contrast-enhanced CT imaging and, if needed, PET-CT or other targeted follow-up procedures or labs based on clinical context.

The primary objectives for both the genetic education and MCED education components are feasibility, acceptability, and fidelity. Feasibility outcomes include completion of germline genetic testing, completion of MCED testing, provision of a testing decision, study enrollment, and retention. Acceptability will be measured with the 3-item Client Satisfaction Questionnaire (CSQ-3). Fidelity will be assessed only in the telephone education arm using session checklists evaluating adherence to planned content and duration; selected sessions will be audio-recorded to validate checklist completion and monitor adherence. Exploratory aims will summarize patient-reported outcomes related to genetic risk, genetic testing, and MCED testing, with no formal hypothesis testing planned for these exploratory analyses.

The study defines the intervention as feasible if at least 30% of enrolled participants complete germline genetic testing and at least 30% complete MCED testing. Enrollment feasibility will be considered promising if at least 60% of eligible participants enroll, and decision-making feasibility if at least 60% of enrolled participants provide a testing decision. Retention will be considered promising if at least 60% of enrolled participants complete follow-up. Acceptability will be considered adequate if the mean CSQ-3 score is at least 3, and fidelity will be considered adequate if at least 90% of participants in the telephone arm complete a session in which at least 90% of required educational content is reviewed.

Study activities are conducted primarily remotely. Recruitment will use social media advertisements and outreach through PanCAN, Dana-Farber Cancer Institute, Boston-area community health clinics, and community organizations serving target populations. Participant-related data, including screening information, surveys, and test results, will be stored in a secure password-protected REDCap database with access restricted to study personnel. Participants will be assigned unique study IDs, and no data or specimens will be banked as part of this study. The protocol anticipates no greater than minimal risk, although risks include distress related to genetic findings, blood draw-related discomfort, questionnaire-related emotional distress, false-positive MCED results, and risks related to follow-up procedures and labs after a positive MCED result.

The expected duration of participation is approximately 6 to 9 months and includes consent, baseline assessment, education, specimen return and testing, result disclosure, and follow-up. All participants, including those who decline testing, will be asked to complete a follow-up survey 3 to 4 months after their last study step. Enrollment is expected to take about 18 months.