A Phase 2 interventional study of Surgical resection and Ommaya/VPS in Medulloblastoma, sponsored by St. Jude Children's Research Hospital. Recruiting at 10 sites in United States. Open to participants aged Up to 59 Months. Per ClinicalTrials.gov, last updated 2026-09-15.
Sponsored by St. Jude Children's Research Hospital · Phase 2, Interventional, and Treatment
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.
The objectives of this study are:
Primary Objectives
Secondary Objectives
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.
Patients on S-2 will receive 8 courses of chemotherapy consisting of:
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 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:
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.
317 studies on the registry are indexed under Medulloblastoma; 51 are open to participants now.
This study's planned enrollment of 130 is above the median of 31 across 255 interventional studies indexed under Medulloblastoma.
Browse Medulloblastoma studies →St. Jude Children's Research Hospital is the lead sponsor of 440 studies on the registry; 102 are open to participants now.
Of its 61 completed or terminated interventional studies of FDA-regulated products, 37 (61%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria - Screening Phase (All Patients)
Participant meets one of the following criteria at the time of screening:
Exclusion Criteria - Screening Phase
Inclusion Criteria - Study Enrollment (All Patients)
Participant must be \< 60 months of age at time of enrollment.
Participant must have confirmation of newly diagnosed medulloblastoma per Central Review:
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.
Participant must have adequate organ function prior to study entry, as defined by:
Adequate renal function as defined by a serum creatinine concentration:
Inclusion Criteria - Stratum S-2
Participant must have confirmed diagnosis of the following medulloblastoma molecular group and subgroup per Central Review.
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-NOS
Participant must be \< 36 months of age at time of enrollment
Inclusion Criteria - Stratum N
Participant must have confirmed diagnosis of one of the following medulloblastoma molecular subgroups per Central Review.
Medulloblastoma - Not classified into SHH (i.e., NWNS or indeterminate)
Exclusion Criteria - All Patients
Participant with prior treatment for medulloblastoma, including:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
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
Educational video and games
Other: Educational and Media Intervention
Standard-of-care (SOC) followed by educational video and games
Other: SOC, Educational and Media Intervention
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
All participants enrolled on S-1 will undergo
Also known as: surgical management
Route of administration: Intravenously (IV)
Also known as: MTX, amethopterin
Route of administration: Intravenously (IV)
Also known as: CDDP, cis-DDP, Platinol-AQ®
Route of administration: Intravenously (IV)
Also known as: Oncovin®
Route of administration: Intravenously (IV)
Also known as: Cytoxan®
Route of administration: Intravenously (IV)
Also known as: Paraplatin®
Route of administration: Intravenously (IV)
Also known as: Hycamtin®
Route of administration: Intravenously (IV)
Also known as: VP-16, Vepesid®
Route of administration: subcutaneous (SQ)
Also known as: Udenyca®
Route of administration: subcutaneous (SQ) or Intravenously (IV)
Also known as: GCSF, Neupogen®
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
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.
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.
Route of administration: Intravenously (IV) \& Intra Ventricular (IVT)
Also known as: MTX, amethopterin
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline through 5 years after enrollment
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: Baseline through 5 years after enrollment
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)
Time frame: Baseline through 5 years after enrollment
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).
Time frame: Baseline through 5 years after enrollment
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.
Time frame: Baseline through 6 months after enrollment
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.
Time frame: Baseline through 6 months after enrollment
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.
Time frame: Baseline through 6 months after enrollment
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.
Time frame: Baseline and 6 months after enrollment
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.
Time frame: 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.
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.
Time frame: 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.
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.
Time frame: 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.
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.
Time frame: 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.
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.
Time frame: 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.
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.
Time frame: 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.
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.
Time frame: Beginning on Day 15 of the first course of A or AIVT and B or BIVT (or Day 8 of one course E).
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.
Time frame: Beginning on Day 15 of the first course of A or AIVT and B or BIVT (or Day 8 of one course E).
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.
Time frame: All samples acquired during each course C for domestic patients and patients at St. Jude only.
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.
Time frame: All samples acquired during each course C for domestic patients and patients at St. Jude, only.
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.
Time frame: Day 1 of each course A, AIVT, B, and BIVT.
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.
Time frame: Day 1 of each course A, AIVT, B, and BIVT.
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.
Time frame: Day 1 of each course A, AIVT, B, and BIVT.
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.
Time frame: Day 1 of each course A, AIVT, B, and BIVT.
Plan to share: 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.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
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.
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Studies of the drugs tested here: Methotrexate · Cisplatin · Vincristine · Cyclophosphamide · Carboplatin · Topotecan · Etoposide · Pegfilgrastim · Filgrastim
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