Cancer Health Assessments Reaching Many

Hereditary Cancer Syndrome Clinical Trial

— CHARM  

Official title:

Exome Sequencing in Diverse Populations in Colorado & Oregon

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03426878
• Other study ID #: 2U01HG007292-05
• Secondary ID: 2U01HG007292-05
• Status: Active, not recruiting
• Phase: N/A
• Start date: August 15, 2018
• Est. completion date: December 31, 2023

Study information

• Verified date: June 2022
• Source: Kaiser Permanente
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 967
• Est. completion date: December 31, 2023
• Est. primary completion date: August 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 49 Years

Eligibility

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

Related Conditions & MeSH terms

• Hereditary Cancer Syndrome
• Neoplastic Syndromes, Hereditary

Intervention

Other:
• Modified genetic counseling
After participants at high risk for a hereditary cancer syndrome receive exome sequencing, they will receive modified genetic counseling to help them understand the results.
• Traditional genetic counseling
After participants at high risk for a hereditary cancer syndrome receive exome sequencing, they will receive traditional genetic counseling to help them understand the results.

Locations

Country	Name	City	State
United States	Denver Health	Denver	Colorado
United States	Kaiser Permanente Center for Health Research	Portland	Oregon

Sponsors (9)

Lead Sponsor	Collaborator
Kaiser Permanente	Columbia University, Dana-Farber Cancer Institute, Denver Health and Hospital Authority, Emory University, National Human Genome Research Institute (NHGRI), Seattle Children's Hospital, University of California, San Francisco, University of Washington

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Positive findings for hereditary cancer syndromes	Number of people found to have a pathogenic variant in one of the cancer genes associated with Lynch syndrome or hereditary breast and ovarian cancer	Within one month of specimen receipt at the laboratory
Secondary	Positive findings for other medically actionable genetic conditions	Number of people with pathogenic variants found in genes related to medically actionable hereditary conditions	Within one month of specimen receipt at the laboratory
Secondary	Positive findings for a selected list of carrier conditions	Number of people with pathogenic variants found in genes related to common carrier conditions	Within one month of specimen receipt at the laboratory
Secondary	Comparison of Healthcare Utilization measured via Electronic Medical Record (EMR) data	Downstream healthcare utilization of specific recommended procedures (e.g., colonoscopy, mammography, surgery) will be compared between participants in the traditional genetic counseling arm, the modified genetic counseling arm, and patients at high risk for a hereditary cancer syndrome that do not join the study (usual care)	Within 12 months of participant receiving information about their hereditary cancer syndrome risk
Secondary	Participant understanding of recommended care	Measurement of participant's understanding of the recommended care based on their genetic test result will be assessed using a validated survey tool	2 weeks post result disclosure, 6 months post result disclosure
Secondary	Participant understanding of genetic test results	Measurement of patient's understanding of the genetic test results will be assessed using a validated survey tool	2 weeks post result disclosure, 6 months post result disclosure
Secondary	Participant satisfaction of genetic counseling	Measurement of the patient's satisfaction of genetic counseling will be assessed using a validated survey tool	2 weeks post result disclosure, 6 months post result disclosure
Secondary	Family communication	Measurement of the degree to which participants shared their genetic test results with various family members will be assessed using a validated survey tool	Baseline, 2 weeks post result disclosure, 6 months post result disclosure
Secondary	Personal utility	Measurement of the participant's perceived utility of obtaining genetic testing and counseling will be assessed using validated survey tools that assess lifestyle behaviors and self-reported health/quality of life.	Baseline, 2 weeks post result disclosure, 6 months post result disclosure