Tumor Rebiopsy in Children and Adolescents With Recurrent or Progressive Solid Malignancies
Condition: Tumor, Solid
MeSH terms: Neoplasms
Study type: Observational

Summary: 
      It has been shown that the genomic landscape of tumors can dramatically change at the time of
      disease progression. This suggests that therapies aimed at treating the tumor at diagnosis
      may not be relevant at the time of relapse. Obtaining fresh tissue at the time of relapse
      could facilitate the identification of potential targets that have developed through
      mutational evolution of the primary tumor and would provide an unprecedented opportunity to
      expand the library of patient derived xenografts (PDX) that are available for comprehensive
      preclinical testing in the setting of relapsed disease.

      The purpose of this observational study is to prospectively collect fresh tumor tissue from
      pediatric patients with solid tumors who have recurrent or progressive disease and submit
      this tissue for comprehensive genomic analysis using clinically available CLIA-certified
      platforms that include WGS, WES and RNAseq, and to assess the reasons for a patient and/or a
      parent for making a decision to proceed with or refuse a re-biopsy procedure in the presence
      of a recurrent or progressive solid tumor. The data obtained will be used to develop new
      novel therapies that incorporate new pharmacological agents in pediatric solid tumors.

      PRIMARY OBJECTIVES:

        -  To prospectively collect fresh tumor tissue from pediatric patients with solid tumors
           who have recurrent or progressive disease and submit this tissue for comprehensive
           genomic analysis.

        -  To assess the reasons a patient and/or a parent make the decision to proceed with or
           refuse a re-biopsy procedure in the presence of a recurrent or progressive solid tumor.

      SECONDARY OBJECTIVES:

        -  To estimate refusal and acceptance rates for re-biopsy and the parental/patient
           attitudes towards a re-biopsy.

        -  To estimate the incidence of complications associated with biopsy.

        -  To estimate the percentage of procedures that fail to obtain adequate tissue for genomic
           analysis.
    

Detailed description: 
      This is a prospective, non-therapeutic study with two components: biopsy of tumor for genomic
      studies and prospective assessment of parental factors related to participation. All patients
      at St. Jude Children's Research Hospital (SJCRH) who meet the eligibility criteria will be
      approached for study participation. The re-biopsy is not mandatory and will only be performed
      after the patient and family have consented. A questionnaire to assess the impact and
      perception of an optional/research only biopsy will be administered following the decision
      regarding re-biopsy. For those consenting to the re-biopsy, approximately 4-8 weeks after
      biopsy, the family and patient will be asked to complete a second questionnaire to assess
      decisional regret.

      Participants may repeat participation in this trial with subsequent relapses, provided
      informed consent is obtained prior to each re-biopsy procedure. For those participants who
      consent to repeat participation, all protocol procedures will be repeated.
    

Intervention name(s): Re-biopsy; Questionnaire
Intervention type(s): Procedure; Other
Intervention description(s): For those participants who agree, a biopsy of their tumor to obtain tissue for genetic analysis will be done at the time of relapse or disease progression.; Parents or patients will be asked to complete a questionnaire to assess the impact and perception of an optional/research only biopsy. A second questionnaire will be administered approximately 4-8 weeks after biopsy to assess decisional regret.
Other intervention name(s): Tumor tissue biopsy; Assessment
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        St. Jude Children's Research Hospital patient with a solid tumor malignancy that is
        progressive or recurrent.
      
Biospecimen description: 
      DNA will be extracted from the patient's peripheral blood and tumor samples and RNA will be
      extracted from the tumor sample and whole genome sequencing (WGS), whole exome sequencing
      (WES) and transcriptome sequencing (RNA-Seq) will be performed on Illumina Next Generation
      Sequencers. Both somatic and germline variants (single nucleotide variants, structural
      variants, insertions/deletions, and copy number variants) will be identified using a
      bioinformatics pipeline developed and validated at SJCRH. Separate reports will be generated
      for the somatic lesions and germline lesions. In the event that there is not enough fresh
      tissue to perform WGS, WES and RNAseq will be performed in FFPE material if available.