Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04359758 |
| Other study ID # |
STUDY00001073 |
| Secondary ID |
P30CA051008 |
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 1, 2020 |
| Est. completion date |
November 1, 2021 |
Study information
| Verified date |
January 2024 |
| Source |
Georgetown University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The goal of this pilot randomized controlled trial is to evaluate the impact and efficacy of
a streamlined genetic education and testing intervention for men with prostate cancer.
Eligible men are prostate cancer survivors who meet criteria for genetic counseling referral.
After completing a baseline survey, participants (n=120) are randomized to Streamlined
Genetic Testing (ST) or Usual Care (UC). Participants in ST are able to review genetic
education materials and then proceed directly to genetic testing. Participants in UC will be
provided with a referral for standard individual genetic counseling. Two months after
randomization all participants will be contacted to complete a follow-up survey.
Description:
Genetic testing is part of clinical care for women with breast and ovarian cancer. Guidelines
have led to increasing genetic testing participation among eligible women. Identifying
pathogenic variants (PVs) in cancer susceptibility genes has important treatment, management
and risk reduction implications for patients and their family members. Men are just as likely
as women to carry a PV in a cancer risk gene and men with prostate cancer are at particularly
high risk for carrying a PV. NCCN guidelines recommend germline genetic testing in men with
metastatic prostate cancer or with Gleason 7+ prostate cancer. These guidelines are likely to
expand given recent studies suggesting that 17% of prostate cancer patients may harbor a
cancer susceptibility PV and that current referral criteria miss many of these patients.
Prostate cancer patients with a PV in BRCA1 or BRCA2 (BRCA) have more aggressive prostate
cancers, are at risk for other primary cancers (e.g., male breast and pancreatic) and their
family members are at risk for a variety of cancers. Thus, genetic testing of prostate cancer
patients has implications for treatment, management, and risk reduction for the patient and
his family members.
Despite these benefits and existing referral guidelines, few men with prostate cancer are
tested. This reflects low genetic counseling referral and participation, since men who attend
genetic counseling get tested at the same high rate as women. Low participation is likely due
to underestimation of the personal health relevance of testing and lack of physician genetic
counseling referral. Thus, the requirement to obtain individual genetic counseling prior to
genetic testing may be a barrier to the receipt of guideline consistent genetic testing.
Recent evidence suggests that traditional comprehensive, patient-centered, educationally
focused pre-test genetic counseling often does not match the needs of patients. Further, as
genetic referral guidelines continue to expand, demand for genetic counseling will outstrip
delivery capacity. Thus, alternative approaches that raise awareness and facilitate access to
genetic testing are needed to maximize our ability to extend the benefits of testing to
prostate cancer patients and their family members while at the same time accommodating
increased demand and conserving scarce genetic counseling resources.
We will test a proactive and streamlined pre-test genetic education (ST) print intervention
designed to speed, simplify and target genetic testing delivery for prostate cancer patients.
Participants randomized to ST will have the option to proceed directly to genetic testing
bypassing traditional pre-test genetic counseling. Usual care (UC) participants will be
informed that they meet guidelines for genetic counseling referral and will be provided with
contact information to schedule a standard telephone pre-test genetic counseling session. All
participants with a PV or variant of uncertain significance (VUS) will be scheduled for a
telephone genetic counseling disclosure session. ST participants who are found not to carry a
PV or VUS will have this result disclosed via clinical letter while disclosure for all UC
participants will be per standard clinical care by the genetic counselor by phone. By
proactively identifying eligible patients, providing streamlined information and facilitating
genetic testing, the ST intervention will increase awareness, facilitate informed testing
decisions, remove the barrier of pre-test genetic counseling and improve genetic testing
delivery capacity.
We will enroll eligible prostate patients diagnosed from 2010-2019 who are being followed
within radiation and medical oncology clinics at the MedStar Georgetown University Hospital
and MedStar Washington Hospital Center. Our specific aims are:
1. Evaluate the impact of ST vs. UC on genetic testing uptake. H1.1: Patients randomized to
ST will be more likely to complete genetic testing compared to UC. H1.2: Participants
randomized to ST will make better informed genetic testing decisions (characterized by
high knowledge, risk comprehension and concordance with attitudes) compared to UC. H1.3:
Few patients in the ST arm will opt for traditional genetic counseling prior to testing.
2. Evaluate patient satisfaction and psychosocial outcomes in ST vs. UC. H2.1: Compared to
UC, those randomized to ST will be more satisfied with their genetic testing decision
and will have less decisional regret.
3. Evaluate the impact of ST vs. UC on uptake of cascade testing in unaffected family
members. In exploratory analyses designed to provide effect size estimates, we will
compare the arms on rates of genetic testing in relatives of patients found to carry a
PV.
Gender and Minorities. Participants will be adult men. Given the racial/ethnic breakdown of
the clinics we are recruiting from. We expect that at least 30% of participants will be
members of racial/ethnic minority groups.
Recruitment. Working with our clinical collaborators and the Survey, Recruitment and
Biospecimen Collection Shared Resource (SRBSR) will obtain contact information of potentially
eligible patients from clinical databases and/or the EMR. We will mail an introductory letter
describing the study (from the study MPIs and the patient's physician), opt-out
postcard/phone number, informed consent document and a print version of the baseline survey
to all potentially eligible participants. We will also email electronic versions of these
materials. Two-weeks following this mailing, a research assistant (RA) will call patients who
have neither opted out nor completed the baseline survey. For men who have not returned the
consent document, we will use an IRB-approved verbal consent for completing the baseline
survey and request return of the written consent prior to randomization. Following completion
of print or electronic consent and the baseline survey, the RA will randomize participants.
Men randomized to ST will be sent a priority mail packet with detailed genetic testing
educational material. Men randomized to UC will be mailed a letter informing them that they
meet guidelines for genetic counseling and provided with contact information to schedule a
genetic counseling appointment with a LCCC genetic counselor.
Randomization. Following completion of the baseline survey and consent document, an RA will
randomize participants via computer-generated random numbers in blocks of 8 and a ratio of
1:1. Participants will be notified of their random assignment via letter and email.
Assessments. We will administer baseline (T0) a 1- to 2-month (T1) follow-up
telephone/electronic surveys. Genetic testing uptake will be assessed via clinical records
and basic clinical and demographic information abstracted from the EMR.
Streamlined Testing (ST) Intervention. Men randomized to ST will be sent a priority mail
packet with the ST print education materials and information on how to proceed with genetic
testing. ST participants will have the option of proceeding directly to genetic testing or
scheduling a telephone genetic counseling session. The content of the ST intervention is
described in section 5.0 above.
Usual Care (UC). After completion of the baseline survey, UC participants will be sent a
letter from their physician indicating that they meet eligibility criteria for genetic
testing, recommending that they schedule genetic counseling and providing a contact telephone
number to schedule their session. Patients may opt for free telephone genetic counseling.
Genetic Testing. Participants who opt for genetic testing will be offered a standard
multigene panel of at least 40 genes, including BRCA and genes associated with potential
differential diagnoses (e.g., Lynch syndrome). All testing will be performed by Invitae, a
CLIA certified clinical lab not affiliated with the GLCCC. Invitae offers genetic testing
free of charge to eligible prostate cancer patients. Prior to proceeding with genetic
testing, participants will be required to sign and return a clinical genetic testing consent
form, after which we will mail them an at-home DNA kit for saliva collection which will be
returned directly to Invitae (shipping costs are pre-paid).
Data Analysis: We will characterize participants by comparing them to decliners on key
demographic and clinical variables derived from the EMR. After performing univariate analysis
on dependent variables, we will apply any needed normalizing or variance stabilizing
transformations. We will follow Consort guidelines for Intent-to-Treat analyses (ITT). We
will compare groups at baseline with χ2 and t-tests and will include covariates that are
associated with group (p <0.10) in our final models.
Aim 1: Evaluate the impact of Proactive Streamlined Education and Testing (ST) vs. Usual Care
(UC) on genetic testing. Analysis: H1.1: Patients randomized to ST will be more likely to
complete genetic testing compared to UC. We will use logistic regression to test this
hypothesis. After entering significant covariates, we will add intervention arm to test the
overall intervention effect. H1.2: Participants randomized to ST will make better informed
genetic testing decisions (characterized by high knowledge, risk comprehension and positive
attitudes) compared to UC. Using multiple regression, we will enter control/confounding
variables and intervention to test the impact of group on our informed decision making
outcomes (knowledge, testing attitudes, risk comprehension). H1.3: Few patients in the ST arm
will opt for traditional genetic counseling prior to testing. We will conduct descriptive
analyses describing the proportion of ST participants who opt for genetic counseling vs.
proceed directly to testing vs. opt against testing.
Aim 2: Evaluate patient satisfaction and psychosocial outcomes in ST vs. UC. Analysis: H2.1:
Compared to UC, those randomized to ST will be more satisfied with their genetic testing
decision and will have less decisional regret. After identifying baseline confounders of each
outcome, we will generate linear regression models in which we enter: 1) confounders; 2)
genetic test result (dummy coded to generate comparisons of carriers vs. non-carriers and
non-carriers vs. untested); 3) group assignment. In the event that we have an insufficient
number of PV carriers for these analyses, we will categorize test result into two levels
(tested vs. untested) and evaluate results among PV carriers more descriptively. Results of
Aim 2 analyses will be primarily focused on generating effect size estimates for our planned
trial of newly diagnosed prostate cancer patients.
Aim 3: Evaluate the impact of ST vs. UC on uptake of cascade testing in unaffected family
members. In exploratory analyses designed to provide effect size estimates for our planned
R01, we will use t-test to compare the ST to UC on the number of relatives of PV carriers who
undergo cascade genetic testing.
Power: Power estimates are for 2-tailed tests (α=.05). The study is powered based on our
primary outcome of patient genetic testing uptake. We expect no attrition since data will be
abstracted from clinic records. We will enroll 120 participants in order to attain 80% power
to detect a clinically meaningful increase of 25% in test uptake from 20% in UC to 45% in ST.
For secondary outcomes, assuming 10% attrition, we will have 80% power to detect modest
effect sizes of d=.54 SDs.
