Next Generation Sequencing of Normal Tissues Prospectively in Pediatric Oncology Patients
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Brain Cancer, Brain Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 12/2/2018 |
| Start Date: | August 28, 2015 |
| End Date: | July 1, 2035 |
Genomes for Kids (G4K)
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.
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.
PRIMARY OBJECTIVES:
- To use clinical genomic sequencing to define the prevalence and spectrum of germline
mutations in cancer predisposition genes in children with cancer.
- For those identified with germline mutations, to correlate germline genomic information
with clinical presentation, tumor genomic findings, treatment response, and outcome.
OTHER PRESPECIFIED OBJECTIVES:
- To generate and analyze data describing patient/parent perceptions of genomic
investigations and research at various time points throughout the study.
- To generate and analyze data surrounding the return of genomic sequencing results,
examine patient/parent understanding of these results and assess the impact of results
on patients and families.
- To determine the feasibility and reliability of performing WES and RNA sequencing on
derivatives from formalin-fixed, paraffin-embedded (FFPE) tumor samples alongside the
analysis of matched frozen tumor and germline samples.
For participants who give consent, a normal tissue sample will be obtained and used for WGS,
WES and RNA sequence analysis. A defined list of 150 genes will be analyzed for reporting
using the normal tissue. Once the results of these analyses are available, they will be
disclosed to physicians, patients and parents. Mixed measures approaches will be used to
assess understanding, acceptance and impact of genomic results on patients and parents.
During the course of the study, the investigators anticipate the list of genes to be reported
using normal tissue to change due to advances in the literature or other evidence linking
additional genes to tumor formation and cancer risk, and new lists may be defined.
To assess provider, patient and family understanding and describe the impacts of genomic
testing and return of results, this study will also incorporate administration of surveys and
semi-structured interviews. Surveys and interviews are optional, but will be offered to all
primary SJCRH providers, as well as all eligible participants and parents, regardless of
whether or not they consent to pursue the genomic testing.
A sample of blood or a skin biopsy will be obtained as a source of germline DNA. This sample
is necessary as it is the comparator against which tumor samples are evaluated. Skin biopsies
may be done on patients who have a diagnosis where peripheral blood is likely to be
contaminated by tumor cells.
- To use clinical genomic sequencing to define the prevalence and spectrum of germline
mutations in cancer predisposition genes in children with cancer.
- For those identified with germline mutations, to correlate germline genomic information
with clinical presentation, tumor genomic findings, treatment response, and outcome.
OTHER PRESPECIFIED OBJECTIVES:
- To generate and analyze data describing patient/parent perceptions of genomic
investigations and research at various time points throughout the study.
- To generate and analyze data surrounding the return of genomic sequencing results,
examine patient/parent understanding of these results and assess the impact of results
on patients and families.
- To determine the feasibility and reliability of performing WES and RNA sequencing on
derivatives from formalin-fixed, paraffin-embedded (FFPE) tumor samples alongside the
analysis of matched frozen tumor and germline samples.
For participants who give consent, a normal tissue sample will be obtained and used for WGS,
WES and RNA sequence analysis. A defined list of 150 genes will be analyzed for reporting
using the normal tissue. Once the results of these analyses are available, they will be
disclosed to physicians, patients and parents. Mixed measures approaches will be used to
assess understanding, acceptance and impact of genomic results on patients and parents.
During the course of the study, the investigators anticipate the list of genes to be reported
using normal tissue to change due to advances in the literature or other evidence linking
additional genes to tumor formation and cancer risk, and new lists may be defined.
To assess provider, patient and family understanding and describe the impacts of genomic
testing and return of results, this study will also incorporate administration of surveys and
semi-structured interviews. Surveys and interviews are optional, but will be offered to all
primary SJCRH providers, as well as all eligible participants and parents, regardless of
whether or not they consent to pursue the genomic testing.
A sample of blood or a skin biopsy will be obtained as a source of germline DNA. This sample
is necessary as it is the comparator against which tumor samples are evaluated. Skin biopsies
may be done on patients who have a diagnosis where peripheral blood is likely to be
contaminated by tumor cells.
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.
We found this trial at
1
site
262 Danny Thomas Pl
Memphis, Tennessee 38105
Memphis, Tennessee 38105
(901) 495-3300
Principal Investigator: Kim E. Nichols, MD
Phone: 866-278-5833
St. Jude Children's Research Hospital St. Jude is unlike any other pediatric treatment and research...
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