Clinical trial NCT03426878: Cancer Health Assessments Reaching Many
Official title: Exome Sequencing in Diverse Populations in Colorado & Oregon
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hereditary Cancer Syndrome
Keywords: Lynch syndrome
Hereditary breast and ovarian cancer
Lead sponsor: Kaiser Permanente
Sponsor class: OTHER
Collaborators: name: National Human Genome Research Institute (NHGRI)
name: University of Washington
name: Seattle Children's Hospital
name: University of California, San Francisco
name: Denver Health and Hospital Authority
name: Emory University
name: Dana-Farber Cancer Institute
name: Columbia University
First posted: 2018-02-08
Enrollment: 967
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All participants will receive exome sequencing. The randomization will be into one of two types of genetic counseling - traditional and modified.
Primary purpose: SCREENING

Brief summary: The CHARM (Cancer Health Assessment Reaching Many) study will assess the utility of clinical exome sequencing and how it affects care in diverse populations. The study population includes adults at risk for hereditary cancer syndromes.

The primary objective is to implement a hereditary cancer risk assessment program in healthy 18-49 year-olds in primary care settings within a vertically integrated health delivery system (Kaiser Permanente) and a federal qualified health center (Denver Health). The investigators will assess clinical exome sequencing implementation and interpretation, as well as tailored interactions for low health literacy including a contextualized consent process, and a modified approach to results disclosure and genetic counseling. The investigators will also assess the clinical utility (healthcare utilization and adherence to recommended care) and personal utility of primary and additional results from clinical exome sequencing, and evaluate the ethical and policy implications of considering personal utility of genomic information decisions for health care coverage.

Detailed description: Aim 1. Implement a hereditary cancer risk-assessment program in healthy 18-49-year-old adults in primary care settings, with stakeholder input, and offer exome sequencing to clarify risk.

Aim 1A. Identify and recruit 880 adult participants at-risk of a hereditary cancer syndrome.

Aim 1B: Generate medical exome sequence data and interpret variants. Aim 1C: Disclose findings from medical exome sequencing, incorporate results into the electronic medical record (EMR), and facilitate downstream patient management and coordination of care with the provider.

Aim 1D. Engage stakeholders to tailor and optimize the program in diverse populations.

Aim 2. Evaluate and tailor for diverse populations the critical interactions in the program, including the consent process, choices for reporting additional findings, and the response to results disclosure.

Aim 2A. Design, implement, and assess a contextualized consent process to support informed decision-making about participation in research about medical exome sequencing.

Aim 2B. Design, implement, and compare a novel decision aid in the second half of the study for selecting the optional categories of additional findings with the approach we developed in CSER1 that offered a category checklist.

Aim 2C. Design, implement, and compare a modified (communication-focused) approach to results disclosure, genetic counseling, and decision making with a standard (information-focused) approach.

Aim 3. Evaluate the clinical utility (including personal utility) of using exome sequencing to diagnose individuals with hereditary cancer syndromes and provide additional findings.

Aim 3A: Measure the yield of reportable findings for hereditary cancer syndromes and additional findings.

Aim 3B: Evaluate subsequent healthcare utilization for all study participants and adherence to recommended care among individuals who are identified with a hereditary cancer syndrome in diverse settings.

Aim 3C. Assess the personal utility of exome sequencing, including primary and additional findings.

Aim 4. Address pragmatic and ethical challenges to the integration of genomic medicine into clinical and health systems decision-making.

Aim 4A: Develop and pilot a system that integrates genomic, clinical, and healthcare utilization data to inform clinicians and patients acting on genomic information and to reduce care gaps in patient management.

Aim 4B: Advance the analysis of the ethical and policy implications of incorporating personal utility of genomic information into the decision framework for healthcare coverage.

Eligibility criteria: Inclusion Criteria:

* Kaiser Permanente Northwest or Denver Health patient
* Screens as high risk for a hereditary cancer syndrome via the risk assessment tool algorithms OR have unknown family history on either their mother or father's side of the family (or both)
* No known prior testing for familial mutations predisposing them to Lynch syndrome or hereditary breast and ovarian cancer
* English or Spanish speaker

Exclusion Criteria:

* Participant self-reported prior testing for Lynch syndrome (LS) or Hereditary Breast and Ovarian Cancer (HBOC) syndrome or identified as having previous comprehensive testing via Kaiser Permanente data files
* Not an English or Spanish speaker
* Unable to provide informed consent
* Don't want results placed in their medical record

Primary outcomes:
measure: Positive findings for hereditary cancer syndromes
timeFrame: Within one month of specimen receipt at the laboratory
Secondary outcomes:
measure: Positive findings for other medically actionable genetic conditions
timeFrame: Within one month of specimen receipt at the laboratory
measure: Positive findings for a selected list of carrier conditions
timeFrame: Within one month of specimen receipt at the laboratory
measure: Comparison of Healthcare Utilization measured via Electronic Medical Record (EMR) data
timeFrame: Within 12 months of participant receiving information about their hereditary cancer syndrome risk
measure: Participant understanding of recommended care
timeFrame: 2 weeks post result disclosure, 6 months post result disclosure
measure: Participant understanding of genetic test results
timeFrame: 2 weeks post result disclosure, 6 months post result disclosure
measure: Participant satisfaction of genetic counseling
timeFrame: 2 weeks post result disclosure, 6 months post result disclosure
measure: Family communication
timeFrame: Baseline, 2 weeks post result disclosure, 6 months post result disclosure
measure: Personal utility
timeFrame: Baseline, 2 weeks post result disclosure, 6 months post result disclosure
Other outcomes:
Locations:
city: Denver
country: United States
facility: Denver Health
state: Colorado
city: Portland
country: United States
facility: Kaiser Permanente Center for Health Research
state: Oregon
Study officials:
affiliation: Center for Health Research, Kaiser Permanente Northwest
name: Michael Leo, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Seattle Children's Hospital
name: Benjamin S Wilfond, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mittendorf KF, Lewis HS, Duenas DM, Eubanks DJ, Gilmore MJ, Goddard KAB, Joseph G, Kauffman TL, Kraft SA, Lindberg NM, Reyes AA, Shuster E, Syngal S, Ukaegbu C, Zepp JM, Wilfond BS, Porter KM. Literacy-adapted, electronic family history assessment for genetics referral in primary care: patient user insights from qualitative interviews. Hered Cancer Clin Pract. 2022 Jun 10;20(1):22. doi: 10.1186/s13053-022-00231-3.
citation: Mittendorf KF, Kauffman TL, Amendola LM, Anderson KP, Biesecker BB, Dorschner MO, Duenas DM, Eubanks DJ, Feigelson HS, Gilmore MJ, Hunter JE, Joseph G, Kraft SA, Lee SSJ, Leo MC, Liles EG, Lindberg NM, Muessig KR, Okuyama S, Porter KM, Riddle LS, Rolf BA, Rope AF, Zepp JM, Jarvik GP, Wilfond BS, Goddard KAB; CHARM study team. Cancer Health Assessments Reaching Many (CHARM): A clinical trial assessing a multimodal cancer genetics services delivery program and its impact on diverse populations. Contemp Clin Trials. 2021 Jul;106:106432. doi: 10.1016/j.cct.2021.106432. Epub 2021 May 11.