Solid, Liquid, Central Nervous System Tumors Clinical Trial
Official title:
Genomes for Kids (G4K)
Verified date | December 2023 |
Source | St. Jude Children's Research Hospital |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
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 5000 patients who will be recruited over the next 7 years.
Status | Active, not recruiting |
Enrollment | 5000 |
Est. completion date | July 1, 2035 |
Est. primary completion date | July 1, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A and older |
Eligibility | Inclusion Criteria: - St. Jude patients prospectively identified at the time of study activation with a diagnosed solid or liquid tumor (benign or malignant). - Adequate tissue must be available (e.g. sufficient germline and/or tumor tissue, from which >1 µg DNA and >0.1 µg RNA must be isolated). Patients who have no tumor tissue available may enroll using only germline sample. Exclusion Criteria: - Past history of hematopoietic stem cell transplantation (or other condition that would result in hematopoietic cell DNA failing to match host tissue DNA). - Tumor or germline tissue not meeting the criteria listed above. - Inability or unwillingness of research participant or legal guardian/representative to give written informed consent. - Participants who are unable to read, write or converse fluently in English will be excluded from Prespecified Objectives 3 and 4. |
Country | Name | City | State |
---|---|---|---|
United States | St. Jude Children's Research Hospital | Memphis | Tennessee |
Lead Sponsor | Collaborator |
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St. Jude Children's Research Hospital |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Proportion of parents/participants by perception of genomic testing | Parent/participant perceptions of genomic investigations and research will be assessed using audiotaped conversations and surveys. Results will be summarized by descriptive statistics. | At study end (up to 13 months after last participant enrollment) | |
Other | Number of participants/parents by level of understanding | Research participant/parent understanding of genomic results and the impact of results on research participants and their families will be assessed by analysis of audiotaped conversations and survey results. Results will be summarized by descriptive statistics | At study end (up to 13 months after last participant enrollment) | |
Other | Proportion of successful sequences of formalin-fixed, paraffin-embedded (FFPE) samples | To assess the practicability, proportions of FFPE samples that can be successfully sequenced will be estimated along with a 95% confidence interval. | Approximately 3 months after enrollment | |
Primary | Overall success rate | Success is defined by the combined successes of (1) quality interpretable genomic data are generated from sequencing tumor and germline tissues, and (2) communicating genomic test results to the primary SJCRH oncologist and the patient and his/her parents.
The Binomial proportion of successful performance will be estimated by the sample proportion and the 99% confidence interval based on the normal approximation. Sample size is 400. |
Approximately 3 months after study enrollment | |
Primary | Number and type of somatic genetic variants and germline genetic variants | WGS, WES and RNA sequence data will be used to identify and characterize somatic genetic variants of pathological significance and germline genetic variants associated with increased cancer risk. Descriptive statistics, such as counts and proportions of variants associated with increased cancer risk will be computed within each patient and in each disease type. | Approximately 3-4 months after the germline sample is obtained |