Back to search results

Molecular and Clinical Risk-Directed Therapy for Medulloblastoma in Infants and Young Children

This study is for infants and young children (up to 4 years, 11 months old) who have been newly diagnosed with medulloblastoma, a type of brain tumor. It's a multi-center study looking at different treatment approaches based on the specific characteristics of the tumor. All participants will have surgery to remove as much of the tumor as safely possible. Depending on the tumor type, treatments may include chemotherapy drugs like Methotrexate, Cisplatin, and Vincristine, given intravenously (into a vein). Some patients may also receive Methotrexate directly into the fluid surrounding the brain and spinal cord (IVT-MTX) or a type of radiation called craniospinal irradiation (CSI) with Carboplatin. The main goal is to see how long patients live without their cancer growing or coming back (progression-free survival) with these different treatments. We are also looking at how these treatments affect thinking and learning abilities.

Study design
This is a multi-center, multinational Phase 2 interventional study aiming to enroll 130 participants. It is not specified if it is randomized or blinded.
What's involved
All participants will undergo surgical resection and may receive an Ommaya/VPS (a device to deliver medicine). The study will measure progression-free survival for up to 7 years after enrollment.
Compensation
Not stated in the trial record.
Follow-up
Participants will be followed for progression-free survival for up to 7 years after enrollment, with estimations occurring 2 years after the last patient starts treatment.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT05535166

Molecular and Clinical Risk-Directed Therapy for Infants and Young Children With Newly Diagnosed Medulloblastoma

Recruiting
PHASE2Up to 59InterventionalTreatment
St. Jude Children's Research Hospital
~130 participants
Updated 2026-09-15 on ClinicalTrials.gov
What's tested:Surgical resectionOmmaya/VPSMethotrexateCisplatinVincristineCyclophosphamide

At a glance

Recruiting sites
10 of 10 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
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.
Measured over Up to 7 years after enrollment with PFS estimation occurring 2 years after treatment initiation of last patient
+5 more outcomes measured

Conditions

Medulloblastoma

Explore related trials

MedulloblastomaG3G4NWNSSonic Hedgehog Protein

NCT05535166

Where you'd take part

This study runs at 10 sites. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.

  • C.S. MOTT Children's Hospital, University of Michigan

    Ann Arbor, Michiganstudy coordinator listed

    Recruiting

  • Children's Hospital and Clinics of Minnesota

    Minneapolis, Minnesotastudy coordinator listed

    Recruiting

  • Cook Children's Medical Center

    Fort Worth, Texasstudy coordinator listed

    Recruiting

  • Lucille Packard Children's Hospital Stanford

    Palo Alto, Californiastudy coordinator listed

    Recruiting

  • Orlando Health Arnold Palmer Hospital for Children

    Orlando, Floridastudy coordinator listed

    Recruiting

  • Primary Children's Hospital

    Salt Lake City, Utahstudy coordinator listed

    Recruiting

  • St. Joseph's Children's Hospital

    Tampa, Floridastudy coordinator listed

    Recruiting

  • St. Jude Children's Research Hospital

    Memphis, Tennesseestudy coordinator listed

    Recruiting

Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.

Study leadership

  • Giles W. Robinson, MD · PRINCIPAL_INVESTIGATOR · St. Jude Children's Research Hospital
  • Aditi Bagchi, MD, PhD · PRINCIPAL_INVESTIGATOR · St. Jude Children's Research Hospital

Who to contact

Tabatha E. Doyle, RN
[email protected]
901-595-2544
Email the study team

Opens a ready-to-send draft in your own email app — review before sending.

Want this trial checked against your situation?

Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.

Check eligibility for this trial ~2 min · HIPAA-protected · delete anytime
Eligibility criteria

Inclusion

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.
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.
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:
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.
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

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.
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.

What this trial 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.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.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.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 irradiationBaseline 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 irradiationBaseline 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 irradiationBaseline 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.