Registry Study of Children and Adults Patients With Relapsed, Refractory, or Progressive Sonic Hedgehog Medulloblastoma Harboring U1 Mutation
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 300
- 试验地点
- 2
- 主要终点
- To describe the incidence of the U1 mutation in SHH medulloblastoma subtypes and verify the feasibility of U1 testing. The primary outcome will be detecting the U1 mutation by polymerase chain reaction (PCR) testing or RNA sequencing (RNAseq).
研究概览
简要总结
The purpose of this study is to create a biobank for patients diagnosed with Sonic Hedgehog Medulloblastoma at Baylor College of Medicine/Texas Children's Cancer Center. A biobank is a facility that stores and manages biological samples (such as blood, tissue, or DNA) from individuals, along with detailed health information, for use in medical research to study diseases and develop new treatments. The investigators are requesting participants' permission to add their information and samples to this biobank.
Being in this research study is voluntary; it is the participant's choice. If the participant joins this study, they can still stop at any time.
If the participant decides to participate, the investigators will review the participant's clinical medical records, demographics, treatment history, family history, and imaging. The investigators will also collect biological samples from the participant and the biological parents' buccal swabs (optional).
The participation in this biobank will last about 5 years from the decision to participate.
Why am I being asked to participate? The participant or their child is invited to participate in this study if the participant or their tumor may have a U1 mutation. U1 mutation is associated with an error in the gene that splices the tumor DNA, leading to random splicing that may increase the tumor mutation burden and generate novel tumor neoantigens (targets). Studying the U1 mutation will enable the investigator to design more effective therapies and guide future treatments for patients with relapsed or refractory sonic hedgehog medulloblastoma, thereby improving their outcomes and quality of life. Moreover, the investigators aim to determine whether germline mutations inherited from parents may increase the risk of medulloblastoma in their offspring. The participant will receive no direct benefit from their participation in this study. However, participation in this study may help the investigators better understand SHH Medulloblastomas and benefit other patients in the future.
详细描述
This is a multicenter, retro- and prospective observational cohort registry study. The registry will collect prospective data on children and young adults between ≥3 and ≤50 years of age at diagnosis, who are diagnosed with relapsed, refractory, or progressive SHH medulloblastoma. Patients and their biological parents will be recruited for this study. In addition, retrospective data will be gathered on patients enrolled in the registry to understand prior therapies and treatment courses before enrollment.
The local principal investigators will identify patients diagnosed at registry institutions through their clinical meetings and databases.
Patients diagnosed at non-registry institutions can get information on the registry through various sources, including but not limited to:
Clinicaltrials.gov registry information Texas Children's Cancer Center website Other patients enrolled in the registry Advertising through scientific talks/posters via various consortia, meetings, and patient support groups
Radiology: imaging studies for patients enrolled and treated in Texas Children's Cancer Center/Baylor College of Medicine (BCM) will be saved in their electronic medical records and uploaded to the radiology PACS system as part of their regular clinical care. For patients enrolled from outside treating centers, imaging CDs will be requested and sent by the legal guardian/patient. Personal health information will be redacted. The investigators will assign each CD a unique research acquisition number linked to the study subject. The study subjects will be assigned a unique study identifier, and images will be uploaded by the Texas Children's Radiology Department to the PACS system for reading. Only study-designated personnel will be allowed to access the imaging, and all published data will be de-identified. CDs will be stored in a locked cabinet.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 3 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For Groups 1 and 2, subjects are eligible to be included in the study only if all of the following criteria are met:
- •Age Patients must be ≥ 3 and ≤ 50 years of age at the time of initial diagnosis.
- •Diagnosis Participants must have a diagnosis of SHH medulloblastoma by histologic or molecular criteria at the time of original diagnosis or relapse.
- •Disease status The disease must be recurrent, refractory, or progressive following therapy, including radiotherapy and chemotherapy.
- •Available tumor tissue sample for U1 testing Participants must have available tumor tissue samples to be tested for the U1 mutation.
- •For Group 3, biological parent(s) of a subject participating in Group 1 or 2 are eligible.
排除标准
- •Subjects not meeting the inclusion criteria will be excluded.
研究组 & 干预措施
Group 2
Patients not treated at registry institutions
Group 3
Biological parents of a subject participating in Group 1 or 2
Group 1
Patients treated at registry institutions
结局指标
主要结局
To describe the incidence of the U1 mutation in SHH medulloblastoma subtypes and verify the feasibility of U1 testing. The primary outcome will be detecting the U1 mutation by polymerase chain reaction (PCR) testing or RNA sequencing (RNAseq).
时间窗: Through study completion, an average of 2 years
U1 mutation status, as determined by PCR, will be summarized in the overall sample and within each SHH medulloblastoma subtype with counts and percentages, along with the corresponding 95% confidence intervals. Feasibility Sensitivity, specificity, PPV, NPV, and accuracy of the new RNASeq diagnostic test will be estimated, utilizing PCR as the reference standard. Only complete cases will be utilized in the following estimations. Sensitivity will be estimated as the proportion of true positives out of all positive PCR tests while specificity will be estimated as the proportion of true negatives. Positive predictive value will be estimated as the proportion of true positives out of all positive RNASeq tests. NPV will be estimated as the proportion of true negatives out of all negative RNASeq tests. Finally, accuracy will be estimated as the proportion of true positives and true negatives out of all tests completed.
次要结局
- To collect and compare the outcomes of the different treatment regimens utilized for pediatric and adult patients with recurrent, refractory, or progressive SHH medulloblastoma with and without U1 mutation.(Through study completion, an average of 2 years)
研究者
Mohammad H. Abu Arja
Instructor
Baylor College of Medicine