Genetic Investigation of Cancer Predisposition

• ClinicalTrials.gov Identifier: NCT04620278
• Recruitment Status: Not yet recruiting
• First Posted: November 6, 2020
• Last Update Posted: March 7, 2022
• Sponsor: The University of Texas Health Science Center at San Antonio
• Information provided by (Responsible Party): The University of Texas Health Science Center at San Antonio

Study Description

Brief Summary:

Clinical information and samples (blood, saliva, and tumor) will be collected from patients with multiple cancers and/or a family history of cancer as well as from affected and unaffected relatives; samples will be systematically sequenced and evaluated for candidate driver mutations.

Condition or disease	Intervention/treatment
Genetic Predisposition; Cancer	Genetic: DNA or RNA Sequencing

Detailed Description:

Genetic screening will be performed on DNA (and/or RNA) isolated from collected samples from affected individuals by whole exome sequencing or RNA sequencing using in-house pipeline to identify candidate sequence variants. These variants will be tested for segregation with the phenotype in other relatives (affected/unaffected). Candidate variants will be subjected to additional downstream analysis, to be guided by the actual type of gene/variant.

Study Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 100 participants
• Observational Model: Family-Based
• Time Perspective: Prospective
• Target Follow-Up Duration: 60 Months
• Official Title: Genetic Investigation of Cancer Predisposition
• Estimated Study Start Date: June 2022
• Estimated Primary Completion Date: June 2030
• Estimated Study Completion Date: December 2035

Groups and Cohorts

Intervention Details:

• Genetic: DNA or RNA Sequencing
  Samples will be used for whole exome (DNA) or RNA sequencing

Outcome Measures

Primary Outcome Measures :

1. Identification of Rare Genetic Variant [ Time Frame: through study completion- approximately 6-12 months ]
   Genetic screen detects a mutation that is likely responsible for tumor development
2. Identification of somatic (tumor only) mutation [ Time Frame: through study completion- approximately 6-12 months ]
   Genetic screen detects a mutation that is likely responsible for tumor development
3. Identification of Rare Genetic Variant in family members [ Time Frame: through study completion- approximately 6-12 months ]
   Genetic screen detects a mutation that is likely responsible for tumor development

Secondary Outcome Measures :

1. Identification of clinical spectrum of the disease in families [ Time Frame: through study completion- approximately 6-12 months ]
   Genetic and clinical analysis reveals clinical features not previously assigned to the disease

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Individuals with a family history of cancer or with a personal history of multiple cancers that might suggest increased genetic predisposition, but for which an identifiable susceptibility mutation has not been detected.

Criteria

Inclusion Criteria:

1. Any age

2. Meets at least ONE of the following:

   1. Personal history (with documented diagnosis) of cancer before the age of 50
   2. Personal history of more than one primary cancer
   3. Documented diagnosis of cancer AND family history of that same cancer type or multiple other cancers that do not fit classical criteria of hereditary cancer syndromes
   4. Documented diagnosis of a rare cancer AND family history of rare cancers that do not fit classical criteria of hereditary cancer syndromes
   5. There is the same type of cancer in several generations of a family
   6. Documented diagnosis of multicentric cancers (e.g bilateral cancers in paired organs, or multifocal cancers in single organs) that usually occur as single lesions when presented sporadically
   7. Early onset cancer (before the age of 50, or breast cancer before age 45) AND family history of early onset cancer Capable of providing access to detailed medical records and family history of cancer

Exclusion Criteria:

1. Established genetic diagnosis of a known hereditary cancer syndrome that is compatible with the clinical presentation
2. Incarcerated

Contacts and Locations

Contacts

Contact: Patricia L Dahia, MD, PhD; 210-567-4866; dahia@uthscsa.edu

Locations

United States, Texas

University of Texas Health Science Center

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

The University of Texas Health Science Center at San Antonio

Investigators

• Principal Investigator: Patricia L Dahia, MD, PhD; University of Texas Health at San Antonio

More Information

• Responsible Party: The University of Texas Health Science Center at San Antonio
• ClinicalTrials.gov Identifier: NCT04620278
• Other Study ID Numbers: HSC20200666H
• First Posted: November 6, 2020
• Last Update Posted: March 7, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All information exchanged between the local investigator/referring physician and the PI will be made through the unique identifiers to maintain patient confidentiality
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: Since the age-related penetrance of the disease is not known, it may be many years before an individual changes his/her affection status. Thus, the clinical updates remain open-ended
• Access Criteria: PI will provide coded data to collaborators who have signed an MTA agreement. These collaborators will not have access to identifiable data

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by The University of Texas Health Science Center at San Antonio:

Genetic analysis; Early diagnosis

Additional relevant MeSH terms:

Disease Susceptibility; Genetic Predisposition to Disease; Disease Attributes; Pathologic Processes