Pedi-STAR: Surface Target Antibody-drug Conjugate (ADC) Antigen Expression in Relapsed/Refractory Pediatric Solid and CNS Tumors
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 130
- 试验地点
- 2
- 主要终点
- Antibody-Drug Conjugate (ADC) Target Expression Screening Success Rate [Prospective Cohort]
研究概览
简要总结
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.
详细描述
This is a non-therapeutic feasibility study evaluating the prospective measurement of antibody-drug conjugate (ADC) target antigen expression in pediatric patients with relapsed or refractory solid or CNS tumors. The study aims to characterize ADC antigen expression patterns, compare expression at diagnosis and relapse, and describe real-world utilization and outcomes of ADCs in pediatric tumors.
Participants will be enrolled into two cohorts: a prospective cohort and a retrospective cohort.
The prospective cohort will undergo eligibility screening, enrollment, specimen submission, bulk RNA sequencing screening, followed by immunohistochemistry (IHC) of highly expressed targets, and clinical return of IHC results to their enrolling provider.The retrospective cohort will include participants who have received ADC therapy as part of routine clinical care and will undergo specimen submission, targeted IHC testing, and clinical data collection.
It is expected that about 130 people will take part in this research.
B+ Foundation is helping to support this research by providing study funding.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Screening
- 盲法
- None
入排标准
- 年龄范围
- — 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion Criteria for Prospective Cohort
- •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.
- •Informed consent for participation for adult participants or parental permission for minor participants (with assent as appropriate based on age of participant).
- •Inclusion Criteria for Retrospective Cohort
- •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).
- •Available specimens Tissue block or unstained slides available expected to yield a minimum of 15 total slides OR other specimens expected to result in adequate IHC testing may substitute for tissue above with the approval of the PI or study staff approval designee prior to submission.. 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.
- •Prior receipt of an antibody-drug conjugate (ADC). The ADC may have been received via either commercial supply or as a participant on a clinical trial. The ADC may have been received at any time during a patient's treatment course for relapsed or refractory disease and on or after January 1st, 2011 up to the time of enrollment of the final prospective participant.
排除标准
- •Exclusion Criteria for Prospective Cohort
- •adults who are unable to consent
- •pregnant women
- •incarcerated individuals
研究组 & 干预措施
Prospective Cohort
Participants with relapsed/refractory solid or CNS tumors will undergo eligibility screening, specimen submission, bulk RNA sequencing, and confirmatory IHC testing. IHC results will be returned to the enrolling provider
干预措施: Bulk RNA Sequencing (Diagnostic Test)
Prospective Cohort
Participants with relapsed/refractory solid or CNS tumors will undergo eligibility screening, specimen submission, bulk RNA sequencing, and confirmatory IHC testing. IHC results will be returned to the enrolling provider
干预措施: Immunohistochemistry (IHC) (Diagnostic Test)
Retrospective Cohort
Participants who have received ADC therapy as part of routine clinical care will submit specimens for targeted IHC testing and clinical data collection. No RNA sequencing will be performed, and IHC results will not be returned
干预措施: Immunohistochemistry (IHC) (Diagnostic Test)
结局指标
主要结局
Antibody-Drug Conjugate (ADC) Target Expression Screening Success Rate [Prospective Cohort]
时间窗: Week 6
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.
次要结局
- ADC Target Antigen Expression Rate by Bulk RNA Sequencing [Prospective Cohort](Week 4)
- ADC Target Antigen Expression Rate by Immunohistochemistry (IHC) [Prospective Cohort](Week 6)
- ADC Target Antigen Transcript Expression Levels by Histologic Diagnosis [Prospective Cohort](Week 4)
- ADC Target Antigen Protein Expression Levels by Histologic Diagnosis [Prospective Cohort](Week 6)
- Change in ADC Target Antigen Transcript Expression Level from Diagnosis to Relapse [Prospective Cohort](48 months)
- Change in ADC Target Antigen Protein Expression Level from Diagnosis to Relapse [Prospective Cohort](48 months)
- ADC Treatment Rate [Prospective Cohort](48 months)
- ADC Therapy Response Rate [Prospective Cohort](48 months)
- ADC Therapy Response Rate [Retrospective Cohort](48 months)
研究者
Steven DuBois, MD
Principal Investigator
Dana-Farber Cancer Institute