Next Generation Sequencing of Normal Tissues Prospectively in Pediatric Oncology Patients

Conditions

• Solid, Liquid, Central Nervous System Tumors

Eligibility Criteria

Sex

ALL

Age

N/A - N/A

Healthy Volunteers

Not accepted

Interventions

• Study Introduction Visit — OTHER
  Within 5±3 weeks following arrival at SJCRH, or at the participant/family's convenience, participants will meet with a genetic counselor and clinician, provide information for a family pedigree, undergo a physical and discuss germline testing options. Study introduction materials will be provided. Families interested in the G4K study will be referred to the study nurse or other G4K member and an Informed consent visit will be scheduled.
• Informed Consent Visit — OTHER
  Within 1±3 weeks following the Study Introduction Visit, or at the participant/family's convenience, the research nurse or other study team member will consent the family and collect demographic and medical information. Participants will complete assessment questionnaires.
• Informed Consent Follow-Up Visit — OTHER
  At or after enrollment but before the release of the gerline results, or at the participant/family's convenience, a subset of participants (30-40) will participate in semi-structured interviews.
• Return of Results Conversation — OTHER
  Participants will complete the assessment questionnaires.
• Return of Results Follow-Up Visits — OTHER
  Return of Results Follow-Up Visits will be conducted twice: the first within 8±4 weeks of the Return of Results Conversation, or at the participant/family's convenience, and the second within 28 ± 4 weeks of the Return of Results Conversation or at the participant/family's convenience. At each visit, participants will complete assessment questionnaires. Semi-structured interviews with parents and adolescents will be conducted.
• Blood Sample — PROCEDURE
  For patients who have not previously provided a blood sample, a sample of blood will be obtained as a source of germline DNA.
• Skin Biopsy — PROCEDURE
  After consent, for participants with a diagnosis where peripheral blood is likely to be contaminated by tumor cells, skin biopsies may be done as a source of germline DNA.

Study Details

The development of next generation sequencing (NGS) techniques, including whole genome (WGS), exome (WES) and RNA sequencing has revolutionized the ability of investigators to query the molecular mechanisms underlying tumor formation. Through the Pediatric Cancer Genome Project (PCGP), investigators at St. Jude Children's Research Hospital (SJCRH) have successfully used NGS approaches to evaluate more than 1,000 pediatric cancers ranging from hematologic malignancies to central nervous system (CNS) and non-CNS solid tumors. From these and related studies, it has become clear that genomic approaches can accurately classify tumors into distinct pathologic and prognostic subtypes and detect alterations in cellular pathways that may serve as novel therapeutic targets. Collectively, these studies suggest that by characterizing the genomic make-up of individual tumors, investigators will be able to develop personalized and potentially more effective cancer treatments and/or preventive measures. This protocol was initially enacted to usher NGS approaches into routine clinical care. During the initial phase of the G4K protocol, 310 participants were recruited and enrolled onto the study. Tumor and/or germline sequencing was completed on all 310 patients, with 253 somatic reports generated (representing 96% of the 263 participants for whom tumor tissue was available and analyzed) and 301 germline reports generated (100% of the 301 participants who agreed to the receipt of germline results). Analyses of the study data are ongoing with plans to prepare initial manuscripts within the next several months. Due to the successful initial execution of the G4K protocol, clinical genomic sequencing of tumor and germline samples is now offered as part of standard clinical care for pediatric oncology patients at St. Jude. The G4K protocol has now been revised. With the revision, the study team will record, store and analyze germline and tumor genomic information. Through the collection of these data, we will examine how germline mutations in 150 cancer predisposition genes influence clinical presentation, tumor histology, tumor genomic findings, response to therapy and long-term outcomes. The overall goals of this research are to further define the prevalence, spectrum and heritability of germline variants in these genes and to decipher how germline mutations influence the phenotypes of an expanding array of cancer predisposition syndromes. These studies allow us to provide more accurate genetic counseling and management strategies to future children harboring mutations in these genes. This remains a non-therapeutic study. Investigators anticipate a sample size of approximately 2500 patients who will be recruited over the next 7 years.

Key Dates

Start date

Aug 28, 2015

Status verified

Apr 2026

Primary completion

Dec 31, 2033

Completion

Dec 31, 2038

Study Design

Enrollment

2,500 participants (estimated)

Arms

• Arm: Participants
  St. Jude patients with a diagnosed solid or liquid tumor (benign or malignant) and their biological parents or legally authorized representative. Interventions: Study Introduction Visit, Informed Consent Visit, Informed Consent Follow-Up Visit, Return of Results Conversation, two Return of Results Follow-Up Visits, Tissue Sample (when available), Blood Sample or Skin Biopsy.

Primary Outcome Measure

Overall success rate [ Time Frame: Approximately 3 months after study enrollment ]

Central Contacts

• Kim E. Nichols, MD
  888-226-4343
  [email protected]

Locations (1)

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