This study is looking to learn whether a tumor testing approach can feasibly measure antibody-drug conjugate (ADC) target proteins in children and young adults with relapsed or refractory solid tumors or central nervous system (CNS) tumors.
The tumor testing approach is a two-step tumor profiling process of:
* Screening with bulk RNA sequencing to see which ADC target genes are turned on in the tumor. * Confirmatory immunohistochemistry (IHC) for targets that show positive expression on the RNA screen, to confirm protein expression.
Age 0 - 30 years at time of initial diagnosis of the solid or CNS tumor
Diagnosis of relapsed or refractory solid or CNS tumor, without a limit on the number of prior episodes of relapse. Refractory disease is defined as disease that progresses on standard-of-care upfront therapy or requires salvage therapy due to inadequate response, e.g. bridging chemoimmunotherapy in a patient with high-risk neuroblastoma and poor end-induction response (PEIR).
Life expectancy of at least 12 weeks at the time of enrollment
Available specimens Tissue block or unstained slides available expected to yield a minimum of 30 total slides., OR other specimens expected to result in adequate (1) RNA quantity and quality for sequencing and (2) IHC testing may substitute for tissue requirement above with the approval of the PI or study staff designee approval prior to submission enrollment. Tumor tissue from relapse/progression is preferred, but tumor tissue from diagnosis if obtained prior to neoadjuvant chemotherapy is acceptable if no relapse/progression sample available.Note that this requirement may be reduced to 15 total slides for patients who have already had RNA sequencing performed on their tumor material.
adults who are unable to consent
pregnant women
incarcerated individuals
Parallel
Bulk RNA Sequencing
Diagnostic testTest performed on tumor tissue to measure antibody-drug conjugate (ADC) target expression
Immunohistochemistry (IHC)
Diagnostic testTest performed on tumor tissue to confirm protein expression of antibody-drug conjugate (ADC) target antigens identified by bulk RNA sequencing
Antibody-Drug Conjugate (ADC) Target Expression Screening Success Rate [Prospective Cohort]
ADC target expression screening success rate is defined as the proportion of participants who successfully complete bulk RNA sequencing with interpretable results. If immunohistochemistry (IHC) testing is indicated based on the bulk RNA sequencing results, the participant must also successfully complete IHC testing with interpretable results. If IHC testing is not indicated, no further testing is required. Participants who submit a tissue specimen but do not meet these criteria will be classified as screening failures.
ADC Target Antigen Expression Rate by Bulk RNA Sequencing [Prospective Cohort]
Bulk RNA sequencing is performed on one tumor sample collected from participants with relapsed/refractory CNS or solid tumors. Expression is defined using a predefined threshold of transcripts per million (TPM) ≥3. The ADC target antigen expression rate is the proportion of participants with expression of at least one evaluated ADC target antigen.
ADC Target Antigen Expression Rate by Immunohistochemistry (IHC) [Prospective Cohort]
IHC is performed on one tumor sample collected from participants with relapsed/refractory CNS or solid tumors. Candidate ADC target antigens identified by screening bulk RNA sequencing are evaluated by IHC. Protein expression is assessed using semi-quantitative staining intensity scores (0-3+) and H-scores. The ADC target antigen expression rate is the proportion of participants with expression of at least one evaluated ADC target antigen by IHC.
ADC Target Antigen Transcript Expression Levels by Histologic Diagnosis [Prospective Cohort]
All potential ADC target antigens are evaluated regardless of histologic diagnosis, and transcript expression is quantified using TPM.
ADC Target Antigen Protein Expression Levels by Histologic Diagnosis [Prospective Cohort]
Candidate ADC target antigens identified by screening bulk RNA sequencing are evaluated by IHC. Protein expression is assessed using semi-quantitative staining intensity scores (0-3+) and H-scores, with higher scores indicating greater protein expression
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Dana-Farber Cancer Institute
Lead sponsor
B+ Foundation
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
