Recruiting

Genetic Mutations

Sponsor:

Case Comprehensive Cancer Center

Code:

NCT04860453

Conditions

Discordant Cancers

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

WES via Illumina NextSeq 550 sequencing system

Blood Draw

Skin biopsy

Saliva Sample

Study Details

Brief summary:

The purpose of this study is to identify novel gene mutations which have contributed to significant personal and family history of cancer. Adults with and without cancer will be accrued to the study. Participants qualify to take part in this research study because someone in their family has been diagnosed with or because they themselves have a cancer diagnosis.

Participants' DNA and other clinical information will be obtained from a blood sample in order to study the genetic basis of cancer and related complications. All portions in the DNA that code for proteins (i.e., the exome) will be studied. Participant DNA sample and information about family structure and family medical history and ethnic origin may also be collected to better understand this information. Clinical information will be stored and biological samples, including DNA, will be kept for up to three (3) years after collection for future. Ultimately, once identified, the role of the specific genetics changes in the development of inherited cancer(s) will be characterized.

Conditions

Discordant Cancers

Study ID

NCT04860453

Start date

Nov 17, 2020

Status verified date

Aug, 2025

Completion date

Jul 1, 2028

Anticipated

Primary completion date

Jul 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Affected patient with a family history suggestive of a known hereditary syndrome or meeting NCCN criteria for germline testing and consent to a multicancer panel

--This cohort is meant as a real world control group receiving routine standard of care and is not eligible for WES.
  • Affected patient with a family history of 5 or more discordant cancers in unilateral descent within a 3-generation pedigree.

  • Unaffected family members within such kindreds will be eligible for WES as long as a minimum of 2 affected and 1 unaffected family members consent to WES as trial participants.

Exclusion Criteria:

  • Unable to safely provide a blood sample for genetic testing
  • Unable to receive or decline to receive genetic counselling through the telephone, video conference, or in person
  • Families known to segregate a previously identified high penetrance cancer susceptibility gene identified through routine medical genetics evaluation are not eligible WES
  • Family is not amenable to routine medical genetics SOC genetics evaluation.

Study Design

Enrollment

150 participants

Anticipated

Interventions and Outcome Measures

Arms

Affected participants with 5 or more discordant cancers - WES

Affected individuals with a family history of 5 or more discordant cancers in unilateral descent with a 3-generation pedigree will receive SOC CLIA/CAP multicancer panel (DNA collected via blood draw or punch biopsy) to examine monogenic variant diagnostic yield. Eligible participants (families with no mutations and at least 2 affected and 1 non-affected family members) may move forward with WES.

Any identified monogenic variants of interest will be sent to an industry partner with CLIA/CAP certification for validation. A 6-month follow-up visit will take place during which variants will be discussed and participants who underwent gHFI variant counting (those who were not considered a gene candidate) will have results explained. Appropriate genetic counselling, recurrence risk, and additional clinical referrals will be made as necessary

SOC genetic counseling (routine clinical care)

Affected individuals (cancer) with a family history suggestive of a known hereditary syndrome or meeting NCCN criteria for germline testing will receive SOC CLIA/CAP multicancer panel in order to examine monogenic variant diagnostic yield (retrospective data)

This arm would also include prospective participants from the "5 or more discordant cancers" group who DID have a variant identified and therefore did not move on to WES.

Interventions

WES via Illumina NextSeq 550 sequencing system

Sequencing will be performed on an Illumina sequencing system

Blood Draw

Blood draw will be via any University Hospitals Laboratory site and sent at room temperature via courier to the Center for Human Genetics (CHG) Laboratory

Skin biopsy

Skin samples obtained via 3mm punch biopsy will be suspended in cell culture media prepared per CHG routine and sent via courier to the Center for Human Genetics Laboratory

Saliva Sample

Participant will provide a saliva sample which be shipped to University Hospitals Laborator site at room temperature

Primary outcome measure

  • Number of participants with a family history of 5 or more discordant cancers that have monogenic germline variants identifiable with WES sequencing [ Time Frame: At baseline for an average of 1.5 hours ]
  • Number of gHFI variants [ Time Frame: At baseline for an average of 1.5 hours ]
  • Diagnostic yield for monogenic germline variants in two arms [ Time Frame: At baseline for an average of 1.5 hours ]

Central Contacts and Locations

Central contacts

Anna Mitchell, MD PhD

1-800-641-2422CTUReferral@UHhospitals.org

Locations

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

Anna Mitchell, MD, PhD

800-641-2422CTUReferral@UHhospitals.org

Principal Investigator:

Anna Mitchell, MD, PhD

More Information

Sponsor

Case Comprehensive Cancer Center

Last update posted

Sep 3, 2025

Last verified

Aug, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Case Comprehensive Cancer Center on 2025-09-03.