Clinical trial NCT03050268: Familial Investigations of Childhood Cancer Predisposition
Official title: Familial Investigations of Childhood Cancer Predisposition
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: 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
Keywords: Familial cancer
Genetic predisposition
Heritable disease
Cancer risk
Genome analysis
Genetic modifiers
Next generation sequencing (NGS)
Genetic counseling
DNA
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
First posted: 2017-02-10
Enrollment: 3000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants with cancer and their family members who meet the eligibility criteria shown below.

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.

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.

Eligibility 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.

Primary outcomes:
measure: Identification of novel cancer predisposing genes
timeFrame: Up to 20 years following study activation
Secondary outcomes:
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Kim E. Nichols, MD
role: PRINCIPAL_INVESTIGATOR
References: