Memphis, Tennessee 38105


Purpose:

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. Despite recent advances, NGS approaches are not yet routinely used as part of clinical care due to their high cost and technical complexity, as well as the many challenges related to data analysis and translation to the clinical setting. The overarching goal of this protocol is to establish and test processes by which NGS technologies, including WGS, WES and RNA sequencing, can be offered to pediatric oncology patients undergoing treatment at SJCRH. This is a non-therapeutic study examining the feasibility, acceptance and impact of clinical WGS, WES and RNA sequencing in a pediatric oncology setting. Investigators anticipate a sample size of approximately 400 patients and 400-800 biological parents.


Study summary:

PRIMARY OBJECTIVES: - To perform clinical next generation whole genome (WGS), exome (WES), and RNA sequencing on SJCRH pediatric oncology patients prospectively over a 24-month period. - To use WGS, WES and RNA sequence data to identify and characterize somatic genetic variants of pathological significance and germline genetic variants associated with increased cancer risk. OTHER PRESPECIFIED OBJECTIVES: - To generate and analyze data describing the informed consent process and patient/parent perceptions of genomic investigations and research. - 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 tumor and/or normal tissue sample will be obtained and used for WGS, WES and RNA sequence analysis. 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. All tumor samples analyzed via the clinical genomics pipeline will undergo routine clinical pathology testing, which will be run in parallel with this study. Genetic variants deemed reportable by the Clinical Genomics Committee will be considered for return to physicians, patients and parents after several validation steps. Genes from the tumor tissue will be analyzed and those with biological and/or clinical relevance will be reported. A defined list of 63 genes will be analyzed for reporting using normal (germline) tissue. 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.


Criteria:

Inclusion Criteria: - New St. Jude patients prospectively identified at the time of study activation with: - Newly diagnosed solid or liquid tumor (benign or malignant), - Relapsed solid or liquid tumor (benign or malignant), or - Refractory solid or liquid tumor (benign or malignant) - Current St. Jude patients who develop a new mass and undergo a surgical procedure to establish the diagnosis of recurrent disease or a new primary tumor. - Current St. Jude patients who, while on therapy, develop refractory disease and undergo a surgical procedure to palliate symptoms. - 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 with retinoblastoma, diffuse intrinsic pontine glioma, craniopharyngioma, or optic pathway tumors who have no tumor tissue available may enroll using only a 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.


NCT ID:

NCT02530658


Primary Contact:

Principal Investigator
Kim E. Nichols, MD
St. Jude Children's Research Hospital

Kim E. Nichols, MD
Phone: 866-278-5833
Email: referralinfo@stjude.org


Backup Contact:

N/A


Location Contact:

Memphis, Tennessee 38105
United States

Kim E. Nichols, MD
Phone: 866-278-5833
Email: referralinfo@stjude.org

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 18, 2017

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