Relapsed and Progressive Sonic Hedgehog Medulloblastoma With U1 Mutation Registry Study

NCT07242963 | Recruiting

• 1 other identifier: H-56521
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Medulloblastoma Recurrent; Medulloblastoma, Childhood, Recurrent; Medulloblastoma, SHH-activated and TP53 Mutant; Medulloblastoma, SHH-activated and TP53 Wildtype

Keywords

SHH medulloblastoma; medulloblastoma; medulloblastoma Recurrent

Outcome Measures

Primary Outcomes (1)

• 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).

  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.

  Through study completion, an average of 2 years

Secondary Outcomes (1)

• 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

Other Outcomes (1)

• To facilitate somatic and germline tissue testing to understand the unique biology of these rare tumors.

  Through study completion, an average of 3 years

Study Arms (3)

Group 1

Patients treated at registry institutions

Group 2

Patients not treated at registry institutions

Group 3

Biological parents of a subject participating in Group 1 or 2

Eligibility Criteria

• Age: 3 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Group 1 - Patients diagnosed/treated at Texas Children's Hospital (TCH) or one of the participating registry institutions. Group 2 - Patients diagnosed at non-registry institutions (an institution not participating in the registry as a site with IRB approval with BCM/TCH as the coordinating center). Group 3 - Biological parents of patients in Group 1 or 2.

You may qualify if:

• 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.

Sponsors & Collaborators

• Mohammad H. Abu Arja: lead
• Baylor College of Medicine: collaborator
• M.D. Anderson Cancer Center: collaborator

Study Sites (2)

Baylor College of Medicine

Houston, Texas, 77004, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Tumor samples: Tumor samples will be obtained from the residual samples after tumor resection for clinically indicated reasons. Frozen tumor samples and/or formalin-fixed paraffin-embedded tumor (FFPE) samples will be collected whenever available. Buccal samples: Buccal swabs will be collected using self-collection kits. Buccal swab samples will be requested from the patients and biological parents (if enrolled). Blood and cerebrospinal fluid (CSF) samples: Blood samples will be obtained and included for whole genome sequencing and intron detection. For CSF, we will collect existing (leftover) samples for future studies. For research samples, the study requests that the research samples be collected when serum samples are collected for clinical reasons.

MeSH Terms

Conditions

Medulloblastoma; Recurrence

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Murali Chintagumpala, MD

  Baylor College of Medicine

  STUDY CHAIR

• Michael D Taylor, MD, PhD

  Baylor College of Medicine

  STUDY CHAIR

• Mohammad H Abu-Arja, MD, MSc

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mohammad H Abu-Arja, MD, MSc

CONTACT

832-824-0592; mohammad.abuarja@bcm.edu

Ta Tara Rideau

CONTACT

TLRIDEAU@texaschildrens.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Instructor

Study Record Dates

• First Submitted: November 7, 2025
• First Posted: November 21, 2025
• Study Start: September 30, 2025
• Primary Completion (Estimated): December 30, 2035
• Study Completion (Estimated): December 30, 2035
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)