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Familial Investigations of Childhood Cancer Predisposition (SJFAMILY)

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ClinicalTrials.gov Identifier: NCT03050268
Recruitment Status : Recruiting
First Posted : February 10, 2017
Last Update Posted : August 10, 2018
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Brief Summary:

NOTE: This is a research study and is not meant to be a substitute for clinical genetic testing. Families may never receive results from the study or may receive results many years from the time they enroll. If you are interested in clinical testing please consider seeing a local genetic counselor or other genetics professional. If you have already had clinical genetic testing and meet eligibility criteria for this study as shown in the Eligibility Section, you may enroll regardless of the results of your clinical genetic testing.

While it is well recognized that hereditary factors contribute to the development of a subset of human cancers, the cause for many cancers remains unknown. The application of next generation sequencing (NGS) technologies has expanded knowledge in the field of hereditary cancer predisposition. Currently, more than 100 cancer predisposing genes have been identified, and it is now estimated that approximately 10% of all cancer patients have an underlying genetic predisposition.

The purpose of this protocol is to identify novel cancer predisposing genes and/or genetic variants. For this study, the investigators will establish a Data Registry linked to a Repository of biological samples. Health information, blood samples and occasionally leftover tumor samples will be collected from individuals with familial cancer. The investigators will use NGS approaches to find changes in genes that may be important in the development of familial cancer. The information gained from this study may provide new and better ways to diagnose and care for people with hereditary cancer.

PRIMARY OBJECTIVE:

  • Establish a registry of families with clustering of cancer in which clinical data are linked to a repository of cryopreserved blood cells, germline DNA, and tumor tissues from the proband and other family members.

SECONDARY OBJECTIVE:

  • Identify novel cancer predisposing genes and/or genetic variants in families with clustering of cancer for which the underlying genetic basis is unknown.

Condition or disease
Acute Leukemia Adenomatous Polyposis Adrenocortical Carcinoma AML BAP1 Tumor Predisposition Syndrome Carney Complex Choroid Plexus Carcinoma Constitutional Mismatch Repair Deficiency Syndrome Diamond-Blackfan Anemia DICER1 Syndrome Dyskeratosis Congenita Emberger Syndrome Familial Acute Myeloid Leukemia Familial Adenomatous Polyposis Fanconi Anemia Familial Cancer Familial Wilms Tumor Familial Neuroblastoma GIST Hereditary Breast and Ovarian Cancer Hereditary Paraganglioma-Pheochromocytoma Syndrome Hodgkin Lymphoma Juvenile Polyposis Li-Fraumeni Syndrome Lynch Syndrome MDS Melanoma Syndrome Multiple Endocrine Neoplasia Type 1 Multiple Endocrine Neoplasia Type 2 Neuroblastoma Neurofibromatosis Type 1 Neurofibromatosis Type II Nevoid Basal Cell Carcinoma Syndrome Non Hodgkin Lymphoma Noonan Syndrome and Other Rasopathy Overgrowth Syndromes Pancreatic Cancer Peutz-Jeghers Syndrome Pheochromocytoma/Paraganglioma PTEN Hamartoma Tumor Syndrome Retinoblastoma Rhabdoid Tumor Predisposition Syndrome Rhabdomyosarcoma Rothmund-Thomson Syndrome Tuberous Sclerosis Von Hippel-Lindau Disease

Detailed Description:

During the study, blood samples or other healthy tissue will be obtained from participants, as well as medical and family histories. When possible, leftover tumor samples will also be collected. If participants agree to be re-contacted in the future, they will be asked about once each year to update their health information and family history.

A blood sample will be drawn at St. Jude or at a convenient place of the participant's choice. Saliva collection will be obtained if a blood draw is not possible. For participants who are present at St. Jude, saliva collection will generally be performed only once using a saliva collection kit. However, if the first collection is not sufficient for protocol required studies, then additional saliva samples may need to be collected, for up to a total of 5 occurrences. For non St. Jude participants, or participants who do not wish or cannot come to St. Jude, saliva will be collected locally and shipped back to the St. Jude. A skin sample will be performed as a source of germline DNA from participants who have undergone an allogeneic bone marrow transplant and do not have a source of pre-transplant DNA available. A skin sample will only be obtained one time.

The biological samples will be stored in the St. Jude Biorepository. The DNA of the samples will be studied to determine if there are changes in specific genes that might explain the cancers in the participant or their family members. When available, and if consent is given by the participant, previously collected and stored leftover tumor samples, bone marrow samples or stored DNA may be analyzed.

Genetic variants of interest include: 1) mutations in known genes that may have escaped detection through prior clinical genetic testing; 2) coding mutations predicted to disrupt protein function, particularly in genes and pathways known to be associated with cancer; 3) potential mutations in regulatory regions of the genome, as predicted by epigenetic studies. In some cases, individuals with known predisposing mutations exhibit milder, more severe or atypical phenotypes. Family members who harbor a predisposing mutation but are discordant for a cancer phenotype will be selected for cellular and genetic studies. These will include DNA sequencing and possibly also creation and analysis of induce pluripotent stem cells (iPSC), transcriptome or epigenetic analysis.

All samples will be identified by a code after removal of all personal identifiable information. Samples will remain in the repository for current and future study.


Study Type : Observational
Estimated Enrollment : 3000 participants
Observational Model: Family-Based
Time Perspective: Prospective
Official Title: Familial Investigations of Childhood Cancer Predisposition
Actual Study Start Date : April 6, 2017
Estimated Primary Completion Date : March 31, 2037
Estimated Study Completion Date : March 31, 2037

Resource links provided by the National Library of Medicine

Genetic and Rare Diseases Information Center resources: Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Lymphosarcoma Ovarian Cancer Ovarian Epithelial Cancer Hodgkin Lymphoma Neurofibromatosis Neurofibromatosis Type 1 Neurofibroma Neurofibromatosis Type 2 Adrenocortical Carcinoma Fanconi Anemia Congenital Aplastic Anemia Fanconi Syndrome Neuroblastoma Pheochromocytoma Paragangliomas 1 Carotid Body Tumor Rhabdoid Tumor Retinoblastoma Wilms' Tumor Tuberous Sclerosis Bourneville Syndrome Diamond-Blackfan Anemia Familial Adenomatous Polyposis MYH-associated Polyposis Nevoid Basal Cell Carcinoma Syndrome Turcot Syndrome Noonan Syndrome Choroid Plexus Carcinoma Von Hippel-Lindau Disease DICER1-related Pleuropulmonary Blastoma Cancer Predisposition Syndrome Multiple Endocrine Neoplasia Type 1 Li-Fraumeni Syndrome Dyskeratosis Congenita Hoyeraal Hreidarsson Syndrome Peutz-Jeghers Syndrome Multiple Endocrine Neoplasia Type 2 Multiple Endocrine Neoplasia Type 2A Carney Complex PTEN Hamartoma Tumor Syndrome Rothmund-Thomson Syndrome BAP1 Tumor Predisposition Syndrome Juvenile Polyposis Syndrome Hereditary Paraganglioma-pheochromocytoma Deafness-lymphedema-leukemia Syndrome Nephropathic Cystinosis Primary Fanconi Syndrome Neuroepithelioma Soft Tissue Sarcoma Neuroendocrine Tumor Pure Red Cell Aplasia Heart Tumor Schwannoma




Primary Outcome Measures :
  1. Identification of novel cancer predisposing genes [ Time Frame: Up to 20 years following study activation ]
    Probands and cancer affected and unaffected relatives from selected families will be sequenced using Whole Genome Sequencing (WGS) or possibly Whole Exome Sequencing (WES) and analyzed to identify new predisposing genetic variants that co-segregate with the tumor phenotype. Data will be analyzed using annotation and filtering strategies to identify potentially deleterious germline mutations that co-segregate with disease.


Biospecimen Retention:   Samples With DNA
Blood, skin or saliva samples and leftover tumor samples.


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Participants with cancer and their family members who meet the eligibility criteria shown below.
Criteria

NOTE: This is a research study and is not meant to be a substitute for clinical genetic testing. Families may never receive results from the study or may receive results many years from the time they enroll. If you are interested in clinical testing please consider seeing a local genetic counselor or other genetics professional. If you have already had clinical genetic testing and meet eligibility criteria for this study as shown below, you may enroll regardless of the results of your clinical genetic testing.

DEFINITION OF FAMILIAR CANCER FOR THIS PROTOCOL:

In this protocol, the definition of "Familial Cancer" is met if any of the following is present:

  • An individual with a history of cancer diagnosed under 26 years of age who has at least one first, second or third degree relative with a history of cancer diagnosed under 51 years of age; OR
  • An individual who has been diagnosed with more than one cancer, at least one of which was diagnosed under 26 years of age; OR
  • An individual with a clinical or molecular diagnosis of a known cancer predisposition syndrome; OR
  • An individual with a congenital cancer diagnosed before 6 months of age; OR
  • An individual with a rare pediatric cancer or tumor diagnosed before 26 years of age

º Excluding human papilloma virus-associated cervical cancer and non-melanoma skin cancer occurring in adults.

INCLUSION CRITERIA:

  • An individual who meets this protocol's definition of "Familial Cancer," as above.
  • Biologic relatives of an individual meeting this protocol's definition of "Familial Cancer," who are either affected or unaffected by cancer.

EXCLUSION CRITERIA:

  • An inability or unwillingness of the research participant or his/her legally authorized representative (LAR) to provide written informed consent.
  • The participant has received allogeneic bone marrow transplantation and has NO pre-transplant germline (cancer-unaffected) DNA available AND is unwilling to provide a skin sample.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03050268


Contacts
Contact: Chimene Kesserwan, MD 866-278-5833 referralinfo@stjude.org
Contact: Jamie L. Maciaszek, PhD 866-278-5833 referralinfo@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Chimene Kesserwan, MD    866-278-5833    referralinfo@stjude.org   
Principal Investigator: Chimene Kesserwan, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Chimene Kesserwan, MD St. Jude Children's Research Hospital

Additional Information:
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT03050268     History of Changes
Other Study ID Numbers: SJFAMILY
First Posted: February 10, 2017    Key Record Dates
Last Update Posted: August 10, 2018
Last Verified: August 2018

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

Keywords provided by St. Jude Children's Research Hospital:
Familial cancer
Genetic predisposition
Heritable disease
Cancer risk
Genome analysis
Genetic modifiers
Next generation sequencing (NGS)
Genetic counseling
DNA

Additional relevant MeSH terms:
Lymphoma
Syndrome
Leukemia
Carcinoma
Leukemia, Myeloid, Acute
Anemia
Pancreatic Neoplasms
Lymphoma, Non-Hodgkin
Hodgkin Disease
Neuroblastoma
Neoplasms
Carcinoma, Basal Cell
Rhabdomyosarcoma
Neurofibromatoses
Neurofibromatosis 1
Neurofibroma
Wilms Tumor
Retinoblastoma
Colorectal Neoplasms
Nasopharyngeal Neoplasms
Pheochromocytoma
Fanconi Anemia
Fanconi Syndrome
Tuberous Sclerosis
Adrenocortical Carcinoma
Adenomatous Polyposis Coli
Disease Susceptibility
Rhabdoid Tumor
Colorectal Neoplasms, Hereditary Nonpolyposis
Paraganglioma