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AzTrials

MedulloblastomaPhase 2NCT05535166

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

A Phase 2 study testing Surgical resection, Ommaya/VPS and Methotrexate in people with Medulloblastoma, run by St. Jude Children's Research Hospital at 10 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages Up to 59 months
Conditions the study is for
Medulloblastoma
What is being tested?
Surgical resection, Ommaya/VPS and Methotrexate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
130 participants
Where
10 sitesUnited States
Study dates
20 Dec 2022to Jul 2035
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 59 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.
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  • 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:
  • 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.
  • 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

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

10 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Tabatha E. Doyle, RN contact

901-595-2544

tabatha.doyle@stjude.org

10 sites in 1 country

United States10 sites, 10 recruiting

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

    Ann Arbor, Michigan, 48109

    Santhosh Upadhyaya, MD, 734-615-7920, saupadhy@med.umich.edu

    Santhosh Upadhyaya, MD

    Recruiting

  • UT Southwestern Medical Center/Harold C Simmons Comprehensive Cancer Center

    Dallas, Texas, 75235

    Daniel Bowers, MD, 214-456-2382, Daniel.Bowers@UTSouthwestern.edu

    Daniel Bowers, MD

    Recruiting

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

    Sibo Zhao, MD, 682-885-4007, sibo.zhao@cookchildrens.org

    Sibo Zhao, MD

    Recruiting

  • Texas Children's Hospital

    Houston, Texas, 77477

    Murali Chintagumpala, MD, 832-822-4266, mxchinta@texaschildrens.org

    Murali Chintagumpala, MD

    Recruiting

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

    Tabatha E. Doyle, RN, 901-595-2544, tabatha.doyle@stjude.org

    Giles W. Robinson, MD

    Recruiting

  • Children's Hospital and Clinics of Minnesota

    Minneapolis, Minnesota, 55404

    Anne Bendel, MD, 612-813-5913, Anne.Bendel@childrensmn.org

    Anne Bendel, MD

    Recruiting

  • Orlando Health Arnold Palmer Hospital for Children

    Orlando, Florida, 32806

    Avery Wright, DO, 321-841-8588, Avery.Wright@orlandohealth.com

    Avery Wright, DO

    Recruiting

  • Lucille Packard Children's Hospital Stanford

    Palo Alto, California, 94304

    Sonia Partap, MD, MS,, 650-723-5535, spartap@stanford.edu

    Sonia Partap, MD, MS,

    Recruiting

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

    Nicholas Whipple, MD, 801-662-4700, nicholas.whipple@hsc.utah.edu

    Nicholas Whipple, MD

    Recruiting

  • St. Joseph's Children's Hospital

    Tampa, Florida, 33607

    Trisha Larkin, MD, 813-321-6820, Trisha.Larkin@baycare.org

    Trisha Larkin, MD

    Recruiting

Other trials in United States

About this study

Official title: SJiMB21: Phase 2 Study of Molecular and Clinical Risk-Directed Therapy for Infants and Young Children With Newly Diagnosed Medulloblastoma

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.

Read the detailed description

The objectives of this study are:

Primary Objectives

  • To estimate the 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.
  • To estimate the progression free survival of SHH-1 infant (0-2.99 years) medulloblastoma patients treated with systemic HD-MTX-based chemotherapy augmented with IVT-MTX.
  • To estimate the 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.
  • To compare cognitive outcomes among infants (0-2.99 years) and young children (3-4.99 years) treated with systemic chemotherapy only to patients treated with systemic chemotherapy and intra-ventricular chemotherapy or delayed risk- adapted craniospinal irradiation.

Secondary Objectives

  • To investigate change in neurocognitive performance among infants (0-2.99 years) and young children (3-4.99 years) treated for medulloblastoma, and examine the impact of demographic factors (e.g., age at treatment, gender, and socioeconomic status), disease-related factors (e.g., presence of hydrocephalus, posterior fossa syndrome) and variants of proposed treatment regimen (e.g., systemic chemotherapy with or without IVT-MTX, radiation dosimetry to key brain structures, treatment-related ototoxicity) on cognitive late effects.
  • To investigate which familial factors (e.g., family cohesion, family coping with medical management, parent-child interaction style) and environmental factors (e.g., parental verbal abilities, home literacy, adherence with rehabilitative therapies, participation in early intervention, school advocacy) associate with socioeconomic status and examine the impact of these factors on cognitive late effects.
  • To evaluate the feasibility and acceptability of a caregiver education program paired with interactive neurodevelopmental games used to improve parent-child interactions, cognitive and social-emotional functioning in infants undergoing treatment for medulloblastoma. (funded by NCI via the R21CA280187)
  • To estimate the magnitude of change in parent-child interactions following participation in a caregiver education paired with interactive neurodevelopmental games. (funded by NCI via the R21CA280187)
  • To estimate the magnitude of change in cognition and social-emotional development associated with a caregiver education program combined with interactive neurodevelopmental games. (funded by NCI via the R21CA280187)
  • To determine the extent of inter- and intra-patient variability in the plasma pharmacokinetics of high-dose systemic methotrexate, cyclophosphamide, vincristine, and topotecan in infants and young children with medulloblastoma, to assess potential covariates to explain this variability, and to explore associations between clinical effects and methotrexate, cyclophosphamide, vincristine, and topotecan pharmacokinetics.
  • To determine the extent of inter- and intra-patient pharmacokinetic variability of methotrexate in ventricular CSF after intraventricular methotrexate dose administration in infants with medulloblastoma, and to explore associations between methotrexate CSF pharmacokinetics and clinical effects.

All participants enrolled will be treated with systemic chemotherapy post-surgical resection of the tumor. Participants will be assigned to treatment strata based first on tumor molecular group and subgroup assignment [SHH (including SHH-1, SHH-2, SHH-3, SHH-4 and SHH-NOS), G3, G4, (including NWNS NOS, or indeterminate cases] and then by clinical risk stratification (age and metastatic state).

Infants and young children on Stratum S-2 and infants on Stratum S-1 will be treated with chemotherapy-only strategies.

  • Stratum S-2:

Patients on S-2 will receive 8 courses of chemotherapy consisting of:

  • 4 Course A (A1A2A3A4)
  • 2 Course B (B1B2)
  • 2 Course C (C1C2) Courses repeat every 28 days/4 weeks.
  • Stratum S-1:

Patients on S-1 will receive the same systemic chemotherapy regimen as S-2, with the addition of intraventricular (IVT)- MTX, administered via Ommaya reservoir, with each systemic MTX infusion. Each S-1 patient is scheduled to receive 12 doses of IVT-MTX. Each patient on S-1 will also receive 8 courses of combination chemotherapy. (4 Course A with IVT, 2 Course B with IVT and 2 Course C). Courses repeat every 28 days/4 weeks.

  • Stratum N:

Stratum N participants will be treated with post-surgery chemotherapy until 36-months-of age followed by radiation CSI with Boost. There is no defined maximum number of systemic chemotherapy courses in stratum N. The length of chemotherapy (number of courses) will depend on the patient's age at enrollment. The chemotherapy plan for stratum N is divided into 5 sub-cohorts:

  • Age ≥34 months and < 36 months: 4 cycles - 2 cycles (A1A2) prior to radiation and 2 cycles (E1, E2) post-radiation
  • Age: ≥32 to <34 months-old: 4 cycles (A1A2A3A4)
  • Age: ≥30 to <32 months-old: 6 cycles (A1A2A3A4 B1B2)
  • Age: ≥28 to <30-months-old: 8 cycles (A1A2A3A4 B1B2 C1C2)
  • Age: < 28 months-old: 8 cycles + multiple cycles of Course D until 36 months old (A1A2A3A4 B1B2 C1C2 D1D2D3D4…)

Courses A, B, C and E repeat every 28 days/4 weeks and Course D repeats every 42 days.

Prior to radiation therapy, around when stratum N patients achieve 36 months of age, they will be re-stratified onto substratum N-1, N-2 or N-3 based on their response to chemotherapy.

Patients who receive less than or equal to 4 cycles of systemic chemotherapy prior to CSI regardless of their substratum assignment (N-1, N-2 or N-3) will have their radiation therapy augmented by IV carboplatin. Carboplatin will be given to each of these patients 1-4 hours before each radiation fraction is delivered.

Patients enrolled in stratum N who have received only 2 courses of pre-radiation chemotherapy will receive 2 additional courses of adjuvant chemotherapy after completing CSI . The adjuvant chemotherapy consists of Cisplatin, Cyclophosphamide, and Vincristine. Patients who receive equal to 4 courses of systemic chemotherapy prior to CSI will have their radiation therapy augmented by IV carboplatin. The patients receiving more than 4 courses of chemotherapy prior to radiation will not receive additional adjuvant chemotherapy after completing CSI.

Patients will be followed for 84 months following enrollment.

Conditions
Medulloblastoma
Being tested
Surgical resection, Ommaya/VPS, Methotrexate, Cisplatin, Vincristine
Keywords
SJiMB21, Brain Cancer, Brain Tumors in Children, Medulloblastoma Sonic Hedgehog subgroup 1, Medulloblastoma Sonic Hedgehog subgroup 2, Medulloblastoma Sonic Hedgehog subgroup 3, Medulloblastoma Sonic Hedgehog subgroup 4, Medulloblastoma Sonic Hedgehog-not otherwise specified, Medulloblastoma G3, Medulloblastoma G4, Medulloblastoma indeterminate, MLPNet, Neural Net Classification Pipeline, Non-WNT non-SHH medulloblastoma, Posterior fossa syndrome, St. Jude Brain Tumor Studies, Treatment for Brain Tumors in Infants and Young Children, Untreated Childhood Medulloblastoma
Medical subject headings
Medulloblastoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Surgical resectionProcedure or surgery

    Also called surgical management

    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.

  • Ommaya/VPSProcedure or surgery

    Also called surgical management

    All participants enrolled on S-1 will undergo

  • MethotrexateDrug

    Also called MTX, amethopterin

    Route of administration: Intravenously (IV)

  • CisplatinDrug

    Also called CDDP, cis-DDP, Platinol-AQ®

    Route of administration: Intravenously (IV)

  • VincristineDrug

    Also called Oncovin®

    Route of administration: Intravenously (IV)

  • CyclophosphamideDrug

    Also called Cytoxan®

    Route of administration: Intravenously (IV)

  • CarboplatinDrug

    Also called Paraplatin®

    Route of administration: Intravenously (IV)

  • TopotecanDrug

    Also called Hycamtin®

    Route of administration: Intravenously (IV)

  • EtoposideDrug

    Also called VP-16, Vepesid®

    Route of administration: Intravenously (IV)

  • PegfilgrastimDrug

    Also called Udenyca®

    Route of administration: subcutaneous (SQ)

  • FilgrastimDrug

    Also called GCSF, Neupogen®

    Route of administration: subcutaneous (SQ) or Intravenously (IV)

  • IrradiationRadiation

    Also called Radiotherapy

    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.

  • Educational and Media InterventionOther

    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.

  • SOC, Educational and Media InterventionOther

    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.

  • MethotrexateDrug

    Also called MTX, amethopterin

    Route of administration: Intravenously (IV) \& Intra Ventricular (IVT)

Study groups in NCT05535166
Study groupRoleWhat they receive
Stratum S-2ExperimentalPatients with Sonic Hedgehog subgroup 2 (SHH-2), 0-2.99 years, or M0 and 3-4.99 years, will receive systemic high-dose methotrexate (HD-MTX) and conventional chemotherapy. Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
Receives: Procedure: Surgical resection; Drug: Methotrexate; Drug: Cisplatin; Drug: Vincristine; Drug: Cyclophosphamide; Drug: Carboplatin; Drug: Topotecan; Drug: Pegfilgrastim; Drug: Filgrastim
Stratum S-1ExperimentalPatients with SHH-1, SHH-3, SHH-4, or SHH-Not otherwise specified (NOS), 0-2.99 years, will receive intraventricular methotrexate (IVT-MTX) in parallel with systemic HD-MTX and conventional chemotherapy. Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
Receives: Procedure: Surgical resection; Procedure: Ommaya/VPS; Drug: Cisplatin; Drug: Vincristine; Drug: Cyclophosphamide; Drug: Carboplatin; Drug: Topotecan; Drug: Pegfilgrastim; Drug: Filgrastim; Drug: Methotrexate
Stratum NExperimentalPatients with Medulloblastoma (MB) group 3 or group 4 (G3/G4) or MB [including Non-WNT non-SHH medulloblastoma (NWNS) NOS or otherwise indeterminate cases] (0-2.99 years) will receive systemic HD-MTX and conventional chemotherapy only for radiation delaying purposes. At 3 years of age, these patients will receive risk-stratified craniospinal irradiation (CSI). Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Etoposide, Pegfilgrastim, Filgrastim, Radiation
Receives: Procedure: Surgical resection; Drug: Methotrexate; Drug: Cisplatin; Drug: Vincristine; Drug: Cyclophosphamide; Drug: Carboplatin; Drug: Topotecan; Drug: Etoposide; Drug: Pegfilgrastim; Drug: Filgrastim; Radiation: Irradiation
Cognitive Study Group I (educational video and games)ExperimentalEducational video and games
Receives: Other: Educational and Media Intervention
Cognitive Study Group II (standard-of-care control)Active comparatorStandard-of-care (SOC) followed by educational video and games
Receives: Other: SOC, Educational and Media Intervention

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    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.

    Measured: Up to 7 years after enrollment with PFS estimation occurring 2 years after treatment initiation of last patient

  2. Progression free survival of SHH-1 infant (0-2.99 years) medulloblastoma patients treated with systemic HD-MTX-based chemotherapy augmented with IVT-MTX.

    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.

    Measured: Up to 7 years after enrollment with PFS estimation occurring 2 years after treatment initiation of last patient

  3. 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.

    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.

    Measured: Up to 7 years after enrollment with PFS estimation occurring 2 years after treatment initiation of last patient

  4. 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

    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.

    Measured: Baseline through 5 years after enrollment

  5. 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

    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.

    Measured: Baseline through 5 years after enrollment

  6. 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

    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.

    Measured: Baseline through 5 years after enrollment

Secondary outcomes (23)

  1. Change in IQ among infants (0-2.99 years) and young children (3-4.99 years) treated for medulloblastoma

    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). The multiple instruments will be combined across all ages into one measure of standardized Full-Scale IQ. A linear mixed-effects regression model will be used to examine changes in IQ from baseline over time as related to demographic (e.g., age at treatment, gender, and socioeconomic status), disease-related (e.g., presence of hydrocephalus, posterior fossa syndrome), and treatment (e.g., systemic chemotherapy with or without IVT-MTX, radiation dosimetry to key brain structures, treatment-related ototoxicity) factors.

    Measured: Baseline through 5 years after enrollment

  2. Change in executive function among infants (0-2.99 years) and young children (3-4.99 years) treated for medulloblastoma

    This 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 6-10)] will assess behavioral manifestations of executive function. A linear mixed-effects regression model will be used to examine changes in executive function from baseline over time as related to demographic (e.g., age at treatment, gender, and socioeconomic status), disease-related (e.g., presence of hydrocephalus, posterior fossa syndrome), and treatment (e.g., systemic chemotherapy with or without IVT-MTX, radiation dosimetry to key brain structures, treatment-related ototoxicity) factors.

    Measured: Baseline through 5 years after enrollment

  3. Change in health-related quality of life among infants (0-2.99 years) and young children (3-4.99 years) treated for medulloblastoma

    Health-related quality of life will be assessed using the PedsQL (ages 2 and older). A linear mixed-effects regression model will be used to examine changes in health-related quality of life from baseline over time as related to demographic (e.g., age at treatment, gender, and socioeconomic status), disease-related (e.g., presence of hydrocephalus, posterior fossa syndrome), and treatment (e.g., systemic chemotherapy with or without IVT-MTX, radiation dosimetry to key brain structures, treatment-related ototoxicity) factors.

    Measured: Baseline through 5 years after enrollment

  4. Association of familial factors and environmental factors with socioeconomic status

    Socioeconomic status will be measured using the Barratt Simplified Measure of Social Status (BSMSS). Generalized linear models will be used to investigate the association of socioeconomic status with familial factors (e.g., family cohesion, family coping with medical management, parent-child interaction style) and environmental factors (e.g., parental verbal abilities, home literacy, adherence with rehabilitative therapies, participation in early intervention, school advocacy)

    Measured: Baseline through 5 years after enrollment

  5. Association of familial factors and environmental factors with cognitive late effects.

    Linear mixed-effects models will be used to examine changes from baseline over time in cognitive outcomes (as described above) with familiar and environmental factors (as described above).

    Measured: Baseline through 5 years after enrollment

  6. Evaluate family interest in caregiver education combined with interactive neurodevelopmental games.

    The neurocognitive intervention consists of the Working for Kids (WFK) education, which is designed to improve parent understanding of the importance of the early learning environment on brain development, and First Pathways Game (FPG), which are interactive neurodevelopmental games designed for parents to play with their children to strengthen brain pathways for specific skills including communication, problem-solving and social emotional skills, motor skills, math skills and early science learning. Family interest in this intervention will be measured by the proportion of families approached enrolling on study.

    Measured: Baseline through 6 months after enrollment

  7. Evaluate intervention feasibility by measuring the rate of participants completing a caregiver education combined with interactive. neurodevelopmental games.

    The neurocognitive intervention consists of the Working for Kids (WFK) education, which is designed to improve parent understanding of the importance of the early learning environment on brain development, and First Pathways Game (FPG), which is an interactive neurodevelopmental games designed for parents to play with their children to strengthen brain pathways for specific skills including communication, problem-solving and social emotional skills, motor skills, math skills and early science learning. Intervention feasibility will be measured by the proportion of randomized participants completing at least 10 neurodevelopmental games.

    Measured: Baseline through 6 months after enrollment

  8. Evaluate the acceptability of a caregiver education combined with interactive neurodevelopmental games.

    The neurocognitive intervention consists of the Working for Kids (WFK) education, which is designed to improve parent understanding of the importance of the early learning environment on brain development, and First Pathways Game (FPG), which is an interactive neurodevelopmental games designed for parents to play with their children to strengthen brain pathways for specific skills including communication, problem-solving and social emotional skills, motor skills, math skills and early science learning. Acceptability will be measured as the proportion of caregivers reporting benefit from the intervention participation on a satisfaction questionnaire.

    Measured: Baseline through 6 months after enrollment

  9. Magnitude of change in cognition and social-emotional development associated with a caregiver education program combined with interactive neurodevelopmental games.

    Mean six-month change from baseline in cognition and social-emotional development as measured by DAYC-2 (parent interview) will be computed for families randomized to the intervention (described above) and for families randomized to the standard care control group.

    Measured: Baseline and 6 months after enrollment

  10. To characterize the plasma systemic clearance (CL) of cyclophosphamide (CTX) in infants and young children with medulloblastoma.

    Drug plasma concentrations will be simultaneously analyzed with a population pharmacokinetic approach, which permits characterizing typical pharmacokinetics and interindividual variability within the population. We will use a similar approach to what we have used in our previously published manuscripts. Cyclophosphamide CL will be estimated based on serial samples acquired during therapy.

    Measured: Day 9 of the first course of A, AIVT, B or BIVT therapy and Days 4 and 5 of course C or Days 2 and 3 of E.

  11. To characterize the area under the concentration-time curve (AUC0-24h) of carboxyethylphosphoramide (CEPM) in infants and young children with medulloblastoma receiving cyclophosphamide.

    Carboxyethylphosphoramide will be included in above described population pharmacokinetic approach. Based on the results of the population pharmacokinetic analysis, the CEPM AUC0-24h can be calculated.

    Measured: Day 9 of the first course of A, AIVT, B or BIVT therapy and Days 4 and 5 of course C or Days 2 and 3 of E.

  12. To characterize the area under the concentration-time curve (AUC0-24h) of 4-hydroxy-cyclophosphamide (4OHCTX) in infants and young children with medulloblastoma receiving cyclophosphamide.

    In a similar manner to the CEPM AUC0-24h, the 4-hydroxy-cyclophosphamide area under the curve AUC0-24h can be estimated based on the results of the population pharmacokinetic analysis.

    Measured: Day 9 of the first course of A, AIVT, B or BIVT therapy and Days 4 and 5 of course C or Days 2 and 3 of E.

  13. To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in in the plasma systemic clearance (CL) of CTX in infants and young children with medulloblastoma receiving CTX.

    A covariate analysis will be performed to investigate potential associations between the CTX CL pharmacokinetic parameter (outcome measure) and demographics and clinical chemistry data (covariates). Continuous covariates will be implemented according to a power model scaled to the population median covariate value. Categorical covariates will be modeled using an exponential change due to the covariate value. Significant covariates will be selected by using a classic forward/backward stepwise approach, with criteria P values of 0.05 and 0.01 for the forward and backward steps, respectively. Wald tests will be also used to test whether covariates should be kept in the model (criteria p-value<0.05) to explain the inter- and intra-patient variability in CTX CL values in infants and young children with medulloblastoma receiving CTX.

    Measured: Data for CTX from Day 9 of the first course of A, AIVT, B or BIVT therapy and Days 4 and 5 of course C or Days 2 and 3 of E.

  14. To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in CEPM AUC0-24h in infants and young children with medulloblastoma receiving CTX.

    A covariate analysis will be performed to investigate potential associations between the CTX AUC pharmacokinetic parameter (outcome measure) and demographics and clinical chemistry data (covariates). Continuous covariates will be implemented according to a power model scaled to the population median covariate value. Categorical covariates will be modeled using an exponential change due to the covariate value. Significant covariates will be selected by using a classic forward/backward stepwise approach, with criteria P values of 0.05 and 0.01 for the forward and backward steps, respectively. Wald tests will be also used to test whether covariates should be kept in the model (criteria p-value<0.05) to explain the inter- and intra-patient variability in CEPM AUC values in infants and young children with medulloblastoma receiving CTX.

    Measured: Data for CEPM from Day 9 of the first course of A, AIVT, B or BIVT therapy and Days 4 and 5 of course C or Days 2 and 3 of E.

  15. To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in 4OHCTX AUC0-24h in infants and young children with medulloblastoma receiving CTX.

    A covariate analysis will be performed to investigate potential associations between the 4OHCTX AUC pharmacokinetic parameter (outcome measure) and demographics and clinical chemistry data (covariates). Continuous covariates will be implemented according to a power model scaled to the population median covariate value. Categorical covariates will be modeled using an exponential change due to the covariate value. Significant covariates will be selected by using a classic forward/backward stepwise approach, with criteria P values of 0.05 and 0.01 for the forward and backward steps, respectively. Wald tests will be also used to test whether covariates should be kept in the model (criteria p-value<0.05) to explain the inter- and intra-patient variability in 4OHCTX AUC values in infants and young children with medulloblastoma receiving CTX.

    Measured: Data for 4OHCTX from Day 9 of the first course of A, AIVT, B or BIVT therapy and Days 4 and 5 of course C or Days 2 and 3 of E.

  16. To characterize the plasma systemic clearance (CL) of vincristine (VCR) in infants and young children with medulloblastoma.

    As with cyclophosphamide, the vincristine drug plasma concentrations will be analyzed with a population pharmacokinetic approach, which permits characterizing typical pharmacokinetics and interindividual variability within the population. Vincristine CL will be estimated based on serial samples acquired during therapy.

    Measured: Beginning on Day 15 of the first course of A or AIVT and B or BIVT (or Day 8 of one course E).

  17. To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in VCR PK parameter (CL) in infants and young children with medulloblastoma receiving VCR.

    A covariate analysis will be performed to investigate potential associations between the VCR CL pharmacokinetic parameter (outcome measure) and demographics and clinical chemistry data (covariates). Continuous covariates will be implemented according to a power model scaled to the population median covariate value. Categorical covariates will be modeled using an exponential change due to the covariate value. Significant covariates will be selected by using a classic forward/backward stepwise approach, with criteria P values of 0.05 and 0.01 for the forward and backward steps, respectively. Wald tests will be also used to test whether covariates should be kept in the model (criteria p-value<0.05) to explain the inter- and intra-patient variability in VCR CL values in infants and young children with medulloblastoma receiving VCR.

    Measured: Beginning on Day 15 of the first course of A or AIVT and B or BIVT (or Day 8 of one course E).

  18. To characterize the plasma systemic clearance (CL) of topotecan (TPT) in infants and young children with medulloblastoma.

    The topotecan drug plasma concentrations will be analyzed with a population pharmacokinetic approach, which permits characterizing typical pharmacokinetics and interindividual variability within the population. Topotecan CL will be estimated based on serial samples acquired during course C of therapy.

    Measured: All samples acquired during each course C for domestic patients and patients at St. Jude only.

  19. To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in TPT PK parameter (CL) in infants and young children with medulloblastoma receiving TPT.

    A covariate analysis will be performed to investigate potential associations between the TPT CL pharmacokinetic parameter (outcome measure) and demographics and clinical chemistry data (covariates). Also included in this analysis will be concomitant medications given at the same as topotecan (i.e., cyclophosphamide), as well as concomitant adjuvant drugs given within 48 hr of topotecan dose in at least 30% of patients included in the analysis. Continuous covariates will be implemented according to a power model scaled to the population median covariate value. Patient age will be tested according to a Hill equation to reflect potential maturation process. Categorical covariates will be modeled using an exponential change due to the covariate value. Significant covariates will be selected by using a classic forward/backward stepwise approach, and a covariate was considered significant at P<0.05 for the forward addition and at the 0.01 for the backward addition.

    Measured: All samples acquired during each course C for domestic patients and patients at St. Jude, only.

  20. To characterize the plasma systemic methotrexate (MTX) clearance (CL) in infants and young children with medulloblastoma.

    Drug plasma concentrations will be simultaneously analyzed with a population pharmacokinetic approach, which permits characterizing typical pharmacokinetics and interindividual variability within the population. We will use a similar approach to what we have used in our previously published manuscripts. Methotrexate CL will be estimated based on serial samples acquired during the first day of each course of therapy.

    Measured: Day 1 of each course A, AIVT, B, and BIVT.

  21. To characterize the area under the concentration-time curve (AUC0-24h) of 7-hydroxymethotrexate (7OHMTX) in infants and young children with medulloblastoma receiving methotrexate.

    7-hydroxymethotrexate will be included in above described population pharmacokinetic approach. Based on the results of the population pharmacokinetic analysis, the 7OHMTX AUC0-24h will be calculated.

    Measured: Day 1 of each course A, AIVT, B, and BIVT.

  22. To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in MTX PK parameter CL in infants and young children with medulloblastoma receiving MTX.

    A covariate analysis will be performed to investigate potential associations between the MTX pharmacokinetic parameter CL (outcome measure) and demographics and clinical chemistry data (covariates). Continuous covariates will be implemented according to a power model scaled to the population median covariate value. Categorical covariates will be modeled using an exponential change due to the covariate value. Significant covariates will be selected by using a classic forward/backward stepwise approach, with criteria P values of 0.05 and 0.01 for the forward and backward steps, respectively. Wald tests will be also used to test whether covariates should be kept in the model (criteria p-value<0.05) to explain the inter- and intra-patient variability in MTX CL values in infants and young children with medulloblastoma receiving MTX.

    Measured: Day 1 of each course A, AIVT, B, and BIVT.

  23. To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in 7OHMTX PK parameter AUC0-24h in infants and young children with medulloblastoma receiving MTX.

    A covariate analysis will be performed to investigate potential associations between the MTX pharmacokinetic parameter AUC (outcome measure) and demographics and clinical chemistry data (covariates). Continuous covariates will be implemented according to a power model scaled to the population median covariate value. Categorical covariates will be modeled using an exponential change due to the covariate value. Significant covariates will be selected by using a classic forward/backward stepwise approach, with criteria P values of 0.05 and 0.01 for the forward and backward steps, respectively. Wald tests will be also used to test whether covariates should be kept in the model (criteria p-value<0.05) to explain the inter- and intra-patient variability in 7OHMTX AUC values in infants and young children with medulloblastoma receiving MTX.

    Measured: Day 1 of each course A, AIVT, B, and BIVT.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2022
  2. Study start20 Dec 2022
  3. Primary completionJul 2035 (estimated)
  4. Study completionJul 2035 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
130 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05535166
Sponsor's protocol ID
SJiMB21
Other IDs
NCI-2022-07099, R21CA280187
Status last verified
Sep 2026
First submitted
23 Aug 2022
Last updated
15 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
Yes: Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Surgical resection, Ommaya/VPS and Methotrexate in people with Medulloblastoma, run by St. Jude Children's Research Hospital at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 53 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Tabatha E. Doyle, RN (901-595-2544, tabatha.doyle@stjude.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05535166.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.

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