NCT05535166 · St. Jude Children's Research Hospital
Molecular and Clinical Risk-Directed Therapy for Infants and Young Children With Newly Diagnosed Medulloblastoma
What this study is about
This is a multi-center, multinational phase 2 trial that aims to explore the use of molecular and clinical risk-directed therapy in treatment of children 0-4.99 years of age with newly diagnosed medulloblastoma.
View original scientific description
This is a multi-center, multinational phase 2 trial that aims to explore the use of molecular and clinical risk-directed therapy in treatment of children 0-4.99 years of age with newly diagnosed medulloblastoma.
Interventions
PROCEDURE
Surgical resection
All participants enrolled will undergo surgical resection prior to treatment. The maximal resection that can be achieved without undue risk to the patient will be attempted, with decisions about feasibility and extent of resection left to the discretion of the neurosurgeon. In instances where an STR is the best extent of resection achieved prior to start of therapy, a "second-look" surgery may be performed between cycles of chemotherapy after discussion with the principal investigator.
PROCEDURE
Ommaya/VPS
All participants enrolled on S-1 will undergo
DRUG
Methotrexate
Route of administration: Intravenously (IV)
DRUG
Cisplatin
Route of administration: Intravenously (IV)
DRUG
Vincristine
Route of administration: Intravenously (IV)
DRUG
Cyclophosphamide
Route of administration: Intravenously (IV)
DRUG
Carboplatin
Route of administration: Intravenously (IV)
DRUG
Topotecan
Route of administration: Intravenously (IV)
DRUG
Etoposide
Route of administration: Intravenously (IV)
DRUG
Pegfilgrastim
Route of administration: subcutaneous (SQ)
DRUG
Filgrastim
Route of administration: subcutaneous (SQ) or Intravenously (IV)
RADIATION
Irradiation
All participants in stratum N will undergo craniospinal irradiation (CSI) with boost to the primary tumor site once they reach 36 months of age. The dose given is based on the molecular risk group and disease response to chemotherapy as noted in the arm descriptions. The type of radiation used includes conformal radiation therapy (photons) or intensity modulated radiation therapy (IMRT) or proton beam therapy.
OTHER
Educational and Media Intervention
Participants watch a 75-minute caregiver education video program and receive access to interactive games on a smartphone or tablet throughout the optional cognitive study.
OTHER
SOC, Educational and Media Intervention
Standard-of-care (SOC) treatment during main cognitive study. After the one-year serial cognitive evaluation, participants will be offered participation in the cognitive study group I intervention.
DRUG
Methotrexate
Route of administration: Intravenously (IV) \& Intra Ventricular (IVT)
Primary outcome measures
Progression free survival of SHH-2 infant (0-2.99 years) and young child (3-4.99 years) medulloblastoma patients treated with systemic HD-MTX-based chemotherapy only.
Time frame: Up to 7 years after enrollment with PFS estimation occurring 2 years after treatment initiation of last patient
Progression free survival (PFS) will be measured from treatment initiation to the earliest of disease progression or death from any cause in stratum S-2 eligible M0 patients who receive at least 1 dose of the chemotherapy regimen. Patients who have not experienced one of these events will be censored at their last date of contact. The Kaplan-Meier estimate of PFS at two years will be computed. PFS will be compared to St. Jude historical cohorts using hazard ratios with 95% confidence intervals.
Progression free survival of SHH-1 infant (0-2.99 years) medulloblastoma patients treated with systemic HD-MTX-based chemotherapy augmented with IVT-MTX.
Time frame: Up to 7 years after enrollment with PFS estimation occurring 2 years after treatment initiation of last patient
Progression free survival (PFS) will be measured from treatment initiation to the earliest of disease progression or death from any cause in stratum S-1 eligible SHH-1 patients who receive at least 1 dose of the chemotherapy regimen. Patients who have not experienced one of these events will be censored at their last date of contact. The Kaplan-Meier estimate of PFS at two years will be computed. PFS will be compared to St. Jude historical cohorts using hazard ratios with 95% confidence intervals.
Progression free survival of G3/G4 infant (0-2.99 years) medulloblastoma patients treated with systemic chemotherapy and delayed risk-adapted CSI augmented with carboplatin.
Time frame: Up to 7 years after enrollment with PFS estimation occurring 2 years after treatment initiation of last patient
Progression free survival (PFS) will be measured from treatment initiation to the earliest of disease progression or death from any cause in stratum S-N eligible patients who receive at least 1 dose of the chemotherapy regimen. Patients who have not experienced one of these events will be censored at their last date of contact. The Kaplan-Meier estimate of PFS at two years will be computed. PFS will be compared to St. Jude historical cohorts using hazard ratios with 95% confidence intervals.
IQ among infants and young children treated with systemic chemotherapy only compared to patients treated with systemic chemotherapy and intra-ventricular chemotherapy or delayed risk-adapted craniospinal irradiation
Time frame: Baseline through 5 years after enrollment
Change from baseline over time in intellectual function (IQ) will be assessed using different instruments as age appropriate. IQ will be measured in children 0-3:6 years of age using Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-4), in children 3.0-5.11 years of age using Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV), and in children 6-10 years of age using Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V). Longitudinal analyses will be conducted using mixed models.
Executive function among infants and young children treated with systemic chemotherapy only compared to patients treated with systemic chemotherapy and intra-ventricular chemotherapy or delayed risk-adapted craniospinal irradiation
Time frame: Baseline through 5 years after enrollment
Change from baseline over time in executive functions will be assessed using different instruments as age appropriate. The Behavior Rating Inventory of Executive Function \[BRIEF-P (ages 2-5:11) and BRIEF-2 (ages 6-18)\] will assess behavioral manifestations of executive function. Longitudinal analyses will be conducted using mixed models.
Health-related quality of life among infants and young children treated with systemic chemotherapy only compared to patients treated with systemic chemotherapy and intra-ventricular chemotherapy or delayed risk-adapted craniospinal irradiation
Time frame: Baseline through 5 years after enrollment
Changes from baseline over time in health-related quality of life will be assessed using the PedsQL (ages 2 and older). Longitudinal analyses will be conducted using mixed models.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- - Screening Phase (All Patients)
- Participants with presumptive/suspected newly diagnosed medulloblastoma.
- Participant meets one of the following criteria at the time of screening:
- Age \< 36 months OR Age ≥ 36 months and \< 60 months with presumptive/suspected non-metastatic disease
- Participant must have adequate tumor tissue from primary tumor for central review of pathology and molecular classification by methylation and IHC
- Participant must be able to begin treatment as outlined in the protocol within 36 days of definitive surgery (day of surgery is Day 0). In case a second surgery is clinically indicated to remove the residual tumor prior to starting treatment, the second surgery will be considered as the definitive surgery (Day 0).
- Parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines.
Exclusion criteria
- - Screening Phase
- Participants with other clinically significant medical disorders (i.e., serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with the study procedure. Inclusion Criteria - Study Enrollment (All Patients)
- Participant must be \< 60 months of age at time of enrollment.
- Note: Each treatment stratum has additional specific age requirements
- Participant must have confirmation of newly diagnosed medulloblastoma per Central Review:
- Central review includes histopathology, IHC and St. Jude Clinical Genomic Methylation Profiling conducted on MLPNet. If tissue or the extracted DNA does not meet quality control criteria for methylation analysis or if methylation classifier is unable assign molecular group/subgroup within the assigned classifier (MLPNet) parameters, then IHC will be used to define molecular group of these cases. IHC cannot be used to determine molecular subgroup. Therefore, IHC defined SHH patients will be enrolled on Stratum S-1 under "SHH-NOS", and all NWNS and indeterminate molecular group will be enrolled on stratum N.
- Note: Diagnosis of medulloblastoma, as well as group and subgroup assignment, will be done by central pathology review at St. Jude only. No outside testing is allowed for trial enrollment.
- Participant must have disease staged by MRI of the brain and spine and by cytologic examination of CSF\
- and be placed into the following categories:
- M0: no evidence of metastatic disease.
- must include a negative CSF cytology result
- M1: Tumor cells found in the CSF but no other evidence of metastasis
- M2: Intracranial tumor beyond the primary tumor site
- M3: Metastatic disease in the spine
- M4: Extraneural metastatic disease
- \*All participants are to undergo CSF cytologic examination regardless of presence or absence of gross metastatic disease unless procedure is medically contraindicated. CSF is to be obtained by lumbar puncture (LP) performed at least 10 days after surgery. If LP is medically contraindicated, ventricular CSF from a shunt or Ommaya reservoir may be used for staging but this is not the preferred option due to lower sensitivity. If LP is medically contraindicated and the patient doesn't have a shunt or reservoir for CSF sampling, the treating physician should reach out to PI or Co-PI regarding decision on enrollment to SJiMB21. The decision to enroll without CSF cytology will be made on case-by-case basis.
- Note: Participants who have M2 disease and positive CSF will be assigned to M3.
- Note: Participants will be assigned to the highest stage number for which they meet eligibility.
- Note: Treatment stratums may have additional stage requirements.
- Patient must have received no previous radiotherapy, chemotherapy, or other brain tumor-directed therapy other than corticosteroid therapy and surgery.
- Participant must have a Lansky performance score of \> 30 (except for patients with posterior fossa syndrome.
- Participant must have adequate organ function prior to study entry, as defined by:
- Absolute neutrophil counts (ANC) \>750/mm\^3
- Platelet count ≥ 50,000/mm\^3 without support of a platelet transfusion within 7 days
- Hemoglobin ≥8.0 g/dL (with or without support of a blood transfusion).
- Normal liver function as defined by Alanine aminotransferase (ALT) concentration ≤ 3 x 45 U/L and total bilirubin ≤ 3 x 1.0.
- Adequate renal function as defined by a serum creatinine concentration:
- Age - 0 to \<1year; Maximum Serum Creatinine (mg/dl) - Male 0.5; Female 0.5
- Age - 1 to \< 2years; Maximum Serum Creatinine (mg/dl) - Male 0.6; Female 0.6
- Age - 1 to \< 2yearsr; Maximum Serum Creatinine (mg/dl) - Male 0.8; Female 0.8
- Participant's parent or legal guardian has the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines. Inclusion Criteria - Stratum S-2
- Participant must have confirmed diagnosis of the following medulloblastoma molecular group and subgroup per Central Review.
- Medulloblastoma SHH-2
- Participant must meet one of the following criteria at time of enrollment:
- Age \<36 months OR Age ≥ 36 months and \< 60 months with non-metastatic disease (M0) Inclusion Criteria - Stratum S-1
- Participant must have confirmed diagnosis of one of the following medulloblastoma molecular subgroups per Central Review.
- Medulloblastoma SHH-1
- Medulloblastoma SHH-3
- Medulloblastoma SHH-4
- Medulloblastoma SHH-NOS
- Includes medulloblastoma cases that could not be assigned to a molecular subgroup using the DNA methylation classifier, but which are in the SHH group and/or cases defined as SHH by IHC.
- Participant must be \< 36 months of age at time of enrollment
- Note: Patients who are \< 36 months of age, regardless of metastatic status (M0/M+), are eligible for enrollment on stratum S-1. Inclusion Criteria - Stratum N
- Participant must have confirmed diagnosis of one of the following medulloblastoma molecular subgroups per Central Review.
- Medulloblastoma G3
- Medulloblastoma G4
- Medulloblastoma - Not classified into SHH (i.e., NWNS or indeterminate)
- Includes medulloblastoma cases that could not be assigned to a molecular group using the DNA methylation classifier but which are in the NWNS class and/or defined as NWNS by IHC.
- Participant must be \<36 months of age at time of enrollment
- All NWNS patients (M+ and M0) are eligible for enrollment in stratum N Exclusion Criteria - All Patients
- CNS embryonal tumor other than medulloblastoma, for example, patients with diagnosis of Atypical Teratoid/Rhabdoid Tumor (ATRT), PNET, Pineoblastoma, Ependymoma, and ETMR are excluded.
- Participant with prior treatment for medulloblastoma, including:
- Radiotherapy
- Chemotherapy
- Cancer directed immunotherapy
- Targeted agents
- NOTE: Corticosteroid therapy is acceptable; prior treatment with chemotherapy, immunotherapy or targeted agents for non-cancer directed indications are acceptable as long as these have been stopped at least 14 days prior to start of therapy or 2 half-lives from last dose. (i.e., methotrexate for juvenile rheumatoid arthritis, JAK inhibitor therapy for eczema, etc.)
- Participant who is actively receiving any other investigational agents.
- Participant with other clinically significant medical disorders (i.e., serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results.
Where
- Palo Alto, California
- Orlando, Florida
- Tampa, Florida
- Ann Arbor, Michigan
- Minneapolis, Minnesota
- Memphis, Tennessee
- Dallas, Texas
- Fort Worth, Texas
- Houston, Texas
- Salt Lake City, Utah
Collaborators
National Cancer Institute (NCI)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Sep 15, 2026 · Source of record for eligibility and locations