Rare Tumors and Cancer Predisposition in Individuals and Families

NCT ID: NCT05350761

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

500 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-03-10

Study Completion Date

2035-12-31

Brief Summary

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Background:

Some people may be prone to develop cancer for many reasons. Factors that affect their risk include the genes they inherit and the environment they live and work in. Researchers want to learn more about the natural history of cancer.

Objective:

To understand how genes and environmental factors can cause tumors and related conditions.

Eligibility:

People of any age who:

Have tumors of an unusual type, pattern, or number

Have a family member with a history of cancer

Have been exposed to other factors that may increase their risk of cancer

Design:

This study does not involve treatment.

Participants will answer questions about their personal and family medical history. They will give permission for researchers to see their medical records.

Participants may be invited to the NIH Clinical Center for a physical exam. They may give samples including saliva, cheek cells, blood, urine, skin, and/or hair.

Participants with cancer may give bone marrow. A needle will be used to remove a small sample of bone marrow from their hip bone.

Participants may have a biopsy of their tumor.

Participants may have other exams:

Dental

Ear, nose, and throat

Eye

Hearing

Heart function and structure

Participants with cancer may undergo more exams:

A test of how much energy their body uses when resting

A sleep study with a test that measures brain electrical activity. They will have sensors attached to their body while they sleep overnight in a lab.

Imaging scans, such as CT, MRI, a test to measure how dense their bones are (DEXA), and ultrasound.

Participants will have their genes tested. A counsellor will help them understand the results.

Participants will be followed until at least 2035.

Detailed Description

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Study Description: The overall purpose of this study is to comprehensively and longitudinally evaluate the natural history of participants with rare tumors, genetic syndromes, genetic variants, and/or family history consistent with or hypothesized to contribute to predisposition to cancer(s) of interest to DCEG investigators. It will also facilitate evaluation of patients who may be candidates for other NIH Clinical Center (CC) clinical trials. These individuals and families will be evaluated and followed longitudinally to define the clinical spectrum (e.g., disease course, cancer risks, response to therapies, survival) and other phenotypic manifestations associated with rare tumors, genetic variants, and cancer predisposition syndromes.

Objectives:

1. To evaluate and define the clinical spectrum (phenotype), penetrance and natural history of disease in syndromes predisposing to cancer;
2. To evaluate the phenotypes and natural history arising from known -or suspected- pathogenic germline variants in known -or suspected cancer-susceptibility genes;
3. To evaluate potential neoplastic precursor conditions in individuals and families at risk of cancer;
4. To quantify site-specific risks of such tumors in family members;
5. To discover, map, and determine inheritance patterns and functions of cancer susceptibility genes;
6. To identify etiologically or clinically relevant changes to the somatic genome in these patients;
7. To educate and counsel study participants about cancer risk including quantitative risk assessment and communication; prevention and surveillance recommendations; early detection activities; and management recommendations, when known.
8. To facilitate and enhance enrollment in interventional clinical trials within the NCI or other Institutes.

Endpoints:

Primary Endpoint: The general goals of the research conducted under this protocol are to:

1. Discover germline cancer susceptibility genes
2. Define the natural history and clinical spectrum of disease in high risk cancer susceptibility families
3. Define potential precursor states
4. Quantify risks of cancers in family members
5. Identify differences between familial and sporadic neoplasia
6. Identify genetic determinants, environmental risk factors, gene-environment, and gene-gene interactions in high risk families
7. Characterize the somatic genome of tumors from participants.

Secondary Endpoints:

1. Define penetrance of tumors in family members
2. Create full protocols for specific tumors or syndromes based on the pilot studies conducing within this study

Conditions

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Cancer Hereditary Neoplasms Genetic Predisposition to Cancer Environment

Keywords

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Cancer Genes/Genetics Hereditary Neoplasms Environment Natural History

Study Design

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Observational Model Type

FAMILY_BASED

Study Time Perspective

OTHER

Study Groups

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Clinical Center Cohort

includes Proband, Other carriers in family, Family Controls

No interventions assigned to this group

Field Cohort

includes Proband, Other carriers in family, Family Controls

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

Although specific familial syndromes vary in prevalence by sex, race or ethnicity, no one is excluded from participation by sex, gender, race or ethnicity. Since families participate in studies, the sex distribution is essentially balanced, and all ages are included. Minor children below the age of assent are actively studied only when the benefits of participation outweigh the risks.

Affected: An individual who meets any of the following criteria will be eligible to participate in this study:

1. Personal medical history of neoplasia of an unusual type, pattern, or number; or,
2. Known or suspected factor(s) predisposing to neoplasia, either genetic and/or congenital factors (birth defects, metabolic phenotype, chromosomal anomalies or Mendelian traits associated with tumors), environmental exposure (medications, occupation, radiation,

diet, infectious agents, etc.), or unusual demographic features (very young age of onset, multiple tumors, etc.).
3. There is no age restriction; therefore including viable neonates However, children \< 3 years old will not come to the Clinical Center unless clinically indicated until they are \>= 3 years old.
4. Participant or their Legally Authorized Representative (LAR) must sign and date an IRB approved informed consent form (signed on paper or electronically for the Field Cohort / signed on paper for the Clinic Center Cohort)

Unaffected Controls: An individual who meets any of the following criteria will be eligible to participate in this study:

1. Family medical history of neoplasia of an unusual type, pattern, or number; or,
2. Known or suspected factor(s) predisposing to neoplasia, either genetic and/or congenital factors (birth defects, metabolic phenotype, chromosomal anomalies or Mendelian traits associated with tumors), environmental exposure (medications, occupation, radiation,

diet, infectious agents, etc.), or unusual demographic features (very young age of onset, multiple tumors, etc.).
3. There is no age restriction; therefore including viable neonates. However, children \< 3 years old will not come to the Clinical Center unless clinically indicated until they are \>= 3 years old.
4. Participant or their LAR must sign and date an IRB-approved informed consent form (signed on paper or electronically for the Field Cohort / signed on paper for the Clinic Center Cohort)

Personal and family medical history will be verified through questionnaires, interviews, and review of pathology slides and medical records. For familial neoplasms, two or more living affected cases among family members are required. The types of suspected factors predisposing to neoplasia and/or familial tumors under active accrual and study will be investigator- and hypothesis-driven. This approach permits CGB investigators to remain alert to the opportunities afforded by clusters of rare tumors in families and individuals, and to be more responsive to the dynamic research priorities in cancer genetics.

Exclusion Criteria

Affected: An individual who meets any of the following criteria will be excluded from participation in this study:

1. Referred individuals for whom reported diagnoses cannot be verified
2. Inability of the participant or LAR to understand and be willing to sign a written informed consent document.
3. Referred individuals who are eligible for other CGB protocols that are specific to a hereditary cancer syndrome (e.g., Li-Fraumeni Syndrome, Familial Melanoma) Unaffected Controls: An individual who meets any of the following criteria will be excluded

from participation in this study:

1. Referred families for whom reported diagnoses cannot be verified
2. Inability of the participant or LAR to understand and be willing to sign a written informed consent document.
3. Referred families who are eligible for other CGB protocols that are specific to a hereditary cancer syndrome (e.g., Li-Fraumeni Syndrome, Familial Melanoma)
Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sharon A Savage, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status RECRUITING

NIH National Cancer Institute - Shady Grove

Rockville, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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NCI Family Study Referrals

Role: CONTACT

Phone: (800) 518-8474

Email: [email protected]

Sharon A Savage, M.D.

Role: CONTACT

Phone: (240) 276-7241

Email: [email protected]

Related Links

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Other Identifiers

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000678-C

Identifier Type: -

Identifier Source: secondary_id

10000678

Identifier Type: -

Identifier Source: org_study_id