Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT01443468
Other study ID # 110255
Secondary ID 11-C-0255
Status Recruiting
Phase
First received
Last updated
Start date January 17, 2012

Study information

Verified date June 13, 2024
Source National Institutes of Health Clinical Center (CC)
Contact NCI Family Study Referrals
Phone (800) 518-8474
Email ncifamilystudyreferrals@mail.nih.gov
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Background: - Li-Fraumeni syndrome (LFS) is a genetic condition that increases the risk for some types of cancer. LFS may lead to cancer of the bone or connective tissue, breast, and brain. It may also increase the risk for certain types of leukemia and other cancers. The only known cause of LFS is a change (called a mutation ) in a gene known as TP53. However, not all people with LFS have a TP53 mutation. Researchers want to study other possible genetic causes of LFS, and factors that may increase or decrease cancer risk in people with the syndrome. Objectives: - To learn more about the types of cancers that occur in individuals with LFS. - To study the role of the TP53 gene in the development of cancer. - To look for other possible genes that cause LFS - To study the effect of LFS diagnosis on families. - To determine if environmental factors or other genes can change a person s cancer risk associated with LFS. Eligibility: - Individuals with a family or personal medical history of cancers consistent with LFS. - Individuals with a family or personal medical history of cancers that does not meet the diagnosis of LFS, but the history is suggestive for LFS (meets the diagnosis for the so-called Li-Fraumeni like syndrome) - Individuals with certain rare cancers - Individuals with a family or personal history of a TP53 gene mutation, with or without related cancer(s). Design: - Participants will fill out a medical history questionnaire and a family history questionnaire. - Blood samples will be collected for DNA and for storage. Cheek cell samples may be collected if blood cannot be obtained for DNA. Participants can choose to have or not have cancer screening with blood tests, imaging studies, and other exams. - Participants will complete questionnaires about their worries about cancer, stress levels, and coping strategies. Diet and physical activity questionnaires will also be given. Other psychological tests may be given as needed. - Participants will be monitored for several years, with regular followup visits to the National Institutes of Health, if indicated. Any changes in health or cancer status will be recorded.


Description:

Study Description: This is a natural history study involving questionnaires, clinical and research evaluations, clinical and research laboratory tests, review of medical records, and cancer surveillance. This is a prospective long-term study of individuals at high risk of cancer due to Li-Fraumeni Syndrome (LFS) or Li-Fraumeni-Like Syndrome (LFL), using a cohort approach. Enrollees are invited to participate in all aspects of the study but can choose to opt out of specific part(s). Objectives: Primary Objectives: - To ascertain/enroll individuals and families with Li-Fraumeni Syndrome (LFS) and Li-Fraumeni-Like Syndrome (LFL) - To evaluation and define the clinical spectrum and natural history of disease in LFS and LFL - To quantify cumulative cancer risk in individuals with LFS or LFL - To develop a cancer screening program for individuals with LFS or LFL - To investigate the mechanisms of tumorigenesis in LFS-related tumors (e.g., cell proliferation, growth regulation, apoptosis) - To identify genetic determinants, environmental factors, and gene-environment interactions that potentially modify cancer risk in these high-risk individuals - To evaluate the psychological, behavioral, and social functioning effects of LFS on affected individuals and their family members - To explore the plausibility of lifestyle interventions as potential strategies for cancer risk reduction - To create an annotated biospecimen repository of LFS-related for translational, etiologic, and outcomes research Secondary Objectives: -To evaluate specific tumor characteristics, including histologies (e.g., leukemia types, brain tumor types, etc.) of cancers diagnosed in individuals with LFS or LFL. -To evaluate the potential effect of therapeutic radiation and radiation exposure from diagnostic/screening imaging studies on cancer risk. - To provide education, cancer risk assessment, and risk management recommendations for study participants. - To collect clinical data related to the treatment of LFS-related cancers, so that outcome and survival may be evaluated. Endpoints: Primary Endpoint: -Occurrence of cancer in individuals and families with LFS or LFL


Recruitment information / eligibility

Status Recruiting
Enrollment 5000
Est. completion date
Est. primary completion date
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group N/A and older
Eligibility - INCLUSION CRITERIA: - On referral, persons of all ages will be considered for inclusion in the study because of either: - A family or personal medical history of neoplasia consistent with the diagnosis of LFS or LFL; or, - A personal history of a germline TP53 mutation; or, - A first- or second- degree relative of a TP53 mutation carrier, regardless of mutation status; or, - A personal history of three or more LFS-related primary cancers; or, - A personal history of adrenal cortical carcinoma or choroid plexus carcinoma at any age, regardless of family history Personal and family medical history must be verified through questionnaires, interviews, review of medical records and/or review of pathology slides. There are 72 families who have previously enrolled in the pilot study under protocol 78-C-0039. As the eligibility criteria remain the same, these families will be eligible for this protocol and will be invited to sign the new consent. -Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document. For both the Field and Clinical Center Cohort, the PI will ensure that study investigators will identify an appropriate LAR consistent with requirements of Policy 403 and will obtain consent from the LAR as outlined in the consent process before initiating research interventions. -Pregnant women In order to study the lifetime rates of cancer development in all individuals with Li-Fraumeni syndrome, we will need to evaluate what effect pregnancy may have on rate of cancer development both in affected individuals and unaffected family controls. Additionally, some cancers are known to have an increased risk of development in the context of pregnancy and lactation. Exclusion of pregnant women would preclude understanding of these cancer risks for an important subset of the population. Pregnant women are eligible for enrollment on the data collection component of this study. Pregnant women will be included in this study as several endpoints may be assessed during pregnancy; counseling, education, and other minimal risk procedures (i.e. blood draw) may be done. We will postpone full clinical evaluations at the Clinical Center of pregnant women until the subject has recovered post-partum. All screening studies, for women who are pregnant, or breastfeeding will be deferred while the woman is pregnant or breastfeeding. Pregnancy testing will be performed for females of childbearing age prior to imaging studies, and the test results must be negative prior to the scan.. The risk to the fetus and pregnant woman would be no greater than minimal for procedures that are performed. EXCLUSION CRITERIA: - Referred individuals and families whose reported diagnoses cannot be verified - Medical or psychiatric disorder which, in the opinion of the Principal Investigator, would preclude the ability to participate in clinical research - Women who are pregnant will not be eligible for the cancer screening protocol until they recover post-partum. Women participating in the cancer screening protocol will discontinue this component if they become pregnant while on study. Once they recover post-partum, they can continue the cancer screening protocol.

Study Design


Related Conditions & MeSH terms


Locations

Country Name City State
United States National Cancer Institute - Shady Grove Bethesda Maryland
United States National Institutes of Health Clinical Center Bethesda Maryland

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Mai PL, Malkin D, Garber JE, Schiffman JD, Weitzel JN, Strong LC, Wyss O, Locke L, Means V, Achatz MI, Hainaut P, Frebourg T, Evans DG, Bleiker E, Patenaude A, Schneider K, Wilfond B, Peters JA, Hwang PM, Ford J, Tabori U, Ognjanovic S, Dennis PA, Wentzensen IM, Greene MH, Fraumeni JF Jr, Savage SA. Li-Fraumeni syndrome: report of a clinical research workshop and creation of a research consortium. Cancer Genet. 2012 Oct;205(10):479-87. doi: 10.1016/j.cancergen.2012.06.008. Epub 2012 Aug 29. — View Citation

Malkin D. Li-fraumeni syndrome. Genes Cancer. 2011 Apr;2(4):475-84. doi: 10.1177/1947601911413466. — View Citation

Villani A, Tabori U, Schiffman J, Shlien A, Beyene J, Druker H, Novokmet A, Finlay J, Malkin D. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. Lancet Oncol. 2011 Jun;12(6):559-67. doi: 10.1016/S1470-2045(11)70119-X. Epub 2011 May 19. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Prevalence Learn more about the types of cancers that occur in individuals with LFS and the age at which these cancers are usually found ongoing
Primary Multiple measures Explore ways to lower cancer risk ongoing
Primary Multiple measures Explore the typical features of the cancers diagnosed in individuals with LFS ongoing
Primary Multiple measures Explore the psychological and social functioning issues faced by LFS families ongoing
Primary Multiple measures Explore the best ways to look for cancers early in individuals with LFS ongoing
Primary Multiple measures Determine if there is any connection between specific mutations in the TP53 gene and the risk of certain type of cancers ongoing
Primary Multiple measures Determine if there are any environmental factors or other genes that can change a person's cancer risk associated with LFS ongoing
Primary Multiple measures Determine how often a change (mutation) in the TP53 gene is found in families in which LFS is suspected ongoing
See also
  Status Clinical Trial Phase
Completed NCT03826043 - THrombo-Embolic Event in Onco-hematology N/A
Terminated NCT03166631 - A Trial to Find the Safe Dose for BI 891065 Alone and in Combination With BI 754091 in Patients With Incurable Tumours or Tumours That Have Spread Phase 1
Completed NCT01938846 - BI 860585 Dose Escalation Single Agent and in Combination With Exemestane or With Paclitaxel in Patients With Various Advanced and/or Metastatic Solid Tumors Phase 1
Recruiting NCT06058312 - Individual Food Preferences for the Mediterranean Diet in Cancer Patients N/A
Completed NCT03308942 - Effects of Single Agent Niraparib and Niraparib Plus Programmed Cell Death-1 (PD-1) Inhibitors in Non-Small Cell Lung Cancer Participants Phase 2
Recruiting NCT06018311 - Exercising Together for Hispanic Prostate Cancer Survivor-Caregiver Dyads N/A
Withdrawn NCT05431439 - Omics of Cancer: OncoGenomics
Completed NCT01343043 - A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma Phase 1
Completed NCT01938638 - Open Label Phase I Dose Escalation Study With BAY1143572 in Patients With Advanced Cancer Phase 1
Recruiting NCT05514444 - Study of MK-4464 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced/Metastatic Solid Tumors (MK-4464-001) Phase 1
Recruiting NCT02292641 - Beyond TME Origins N/A
Terminated NCT00954512 - Study of Robatumumab (SCH 717454, MK-7454) in Combination With Different Treatment Regimens in Participants With Advanced Solid Tumors (P04722, MK-7454-004) Phase 1/Phase 2
Recruiting NCT04958239 - A Study to Test Different Doses of BI 765179 Alone and in Combination With Ezabenlimab in Patients With Advanced Cancer (Solid Tumors) Phase 1
Recruiting NCT04627376 - Multimodal Program for Cancer Related Cachexia Prevention N/A
Completed NCT01222728 - Using Positron Emission Tomography to Predict Intracranial Tumor Growth in Neurofibromatosis Type II Patients
Recruiting NCT06004440 - Real World Registry for Use of the Ion Endoluminal System
Active, not recruiting NCT05636696 - COMPANION: A Couple Intervention Targeting Cancer-related Fatigue N/A
Not yet recruiting NCT06035549 - Resilience in East Asian Immigrants for Advance Care Planning Discussions N/A
Recruiting NCT06004466 - Noninvasive Internal Jugular Venous Oximetry
Completed NCT02909348 - Immunophenotyping of Melanoma Patients on Treatment With Pembrolizumab