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

NCT05535166 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 3 other identifiers: SJiMB21NCI-2022-07099R21CA280187
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Medulloblastoma

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

Outcome Measures

Primary Outcomes (6)

• 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.

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

• 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.

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

• 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.

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

• 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.

  Baseline through 5 years after enrollment

• 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.

  Baseline through 5 years after enrollment

• 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.

  Baseline through 5 years after enrollment

Secondary Outcomes (23)

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

  Baseline through 5 years after enrollment

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

  Baseline through 5 years after enrollment

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

  Baseline through 5 years after enrollment

• Association of familial factors and environmental factors with socioeconomic status

  Baseline through 5 years after enrollment

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

  Baseline through 5 years after enrollment

Study Arms (5)

Stratum S-2

EXPERIMENTAL

Patients 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

Procedure: Surgical resection; Drug: Methotrexate; Drug: Cisplatin; Drug: Vincristine; Drug: Cyclophosphamide; Drug: Carboplatin; Drug: Topotecan; Drug: Pegfilgrastim; Drug: Filgrastim

Stratum S-1

EXPERIMENTAL

Patients 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

Procedure: Surgical resection; Procedure: Ommaya/VPS; Drug: Cisplatin; Drug: Vincristine; Drug: Cyclophosphamide; Drug: Carboplatin; Drug: Topotecan; Drug: Pegfilgrastim; Drug: Filgrastim; Drug: Methotrexate

Stratum N

EXPERIMENTAL

Patients 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

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)

EXPERIMENTAL

Educational video and games

Other: Educational and Media Intervention

Cognitive Study Group II (standard-of-care control)

ACTIVE COMPARATOR

Standard-of-care (SOC) followed by educational video and games

Other: SOC, Educational and Media Intervention

Interventions

Surgical resection PROCEDURE

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.

Also known as: surgical management

Stratum N; Stratum S-1; Stratum S-2

Ommaya/VPS PROCEDURE

All participants enrolled on S-1 will undergo

Also known as: surgical management

Stratum S-1

Methotrexate DRUG

Route of administration: Intravenously (IV)

Also known as: MTX, amethopterin

Stratum N; Stratum S-2

Cisplatin DRUG

Route of administration: Intravenously (IV)

Also known as: CDDP, cis-DDP, Platinol-AQ®

Stratum N; Stratum S-1; Stratum S-2

Vincristine DRUG

Route of administration: Intravenously (IV)

Also known as: Oncovin®

Stratum N; Stratum S-1; Stratum S-2

Cyclophosphamide DRUG

Route of administration: Intravenously (IV)

Also known as: Cytoxan®

Stratum N; Stratum S-1; Stratum S-2

Carboplatin DRUG

Route of administration: Intravenously (IV)

Also known as: Paraplatin®

Stratum N; Stratum S-1; Stratum S-2

Topotecan DRUG

Route of administration: Intravenously (IV)

Also known as: Hycamtin®

Stratum N; Stratum S-1; Stratum S-2

Etoposide DRUG

Route of administration: Intravenously (IV)

Also known as: VP-16, Vepesid®

Stratum N

Pegfilgrastim DRUG

Route of administration: subcutaneous (SQ)

Also known as: Udenyca®

Stratum N; Stratum S-1; Stratum S-2

Filgrastim DRUG

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

Also known as: GCSF, Neupogen®

Stratum N; Stratum S-1; Stratum S-2

Irradiation RADIATION

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.

Also known as: Radiotherapy

Stratum N

SOC, Educational and Media Intervention OTHER

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.

Cognitive Study Group II (standard-of-care control)

Educational and Media Intervention OTHER

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.

Cognitive Study Group I (educational video and games)

Eligibility Criteria

• Age: Up to 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• National Cancer Institute (NCI): collaborator

Study Sites (10)

Lucille Packard Children's Hospital Stanford

Palo Alto, California, 94304, United States

RECRUITING

Orlando Health Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States

RECRUITING

St. Joseph's Children's Hospital

Tampa, Florida, 33607, United States

RECRUITING

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

Ann Arbor, Michigan, 48109, United States

RECRUITING

Children's Hospital and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

UT Southwestern Medical Center/Harold C Simmons Comprehensive Cancer Center

Dallas, Texas, 75235, United States

RECRUITING

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77477, United States

RECRUITING

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

RECRUITING

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude
• St. Jude Brain Tumor Studies

MeSH Terms

Conditions

Medulloblastoma; Brain Neoplasms

Interventions

Methotrexate; Cisplatin; Vincristine; Cyclophosphamide; Carboplatin; Topotecan; Etoposide; pegfilgrastim; Filgrastim; Radiation; Radiotherapy

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; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Coordination Complexes; Camptothecin; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Physical Phenomena; Therapeutics

Study Officials

• Giles W. Robinson, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

• Aditi Bagchi, MD, PhD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tabatha E. Doyle, RN

CONTACT

901-595-2544; tabatha.doyle@stjude.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2022
• First Posted: September 10, 2022
• Study Start: December 20, 2022
• Primary Completion (Estimated): July 1, 2035
• Study Completion (Estimated): July 1, 2035
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available at the time of article publication.
• Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Locations

US (10)