Brain and Central Nervous System TumorsPhase 2NCT00602667
Risk-Adapted Therapy for Young Children With Embryonal Brain Tumors, Choroid Plexus Carcinoma, High Grade Glioma or Ependymoma
A Phase 2 study testing Induction Chemotherapy, Low-Risk Therapy and High-Risk Therapy in people with Brain and Central Nervous System Tumors, run by St. Jude Children's Research Hospital at 6 sites in 2 countries.
Trial summary
RATIONALE: In this study a combination of anti-cancer drugs (chemotherapy) is used to treat brain tumors in young children. Using chemotherapy gives the brain more time to develop before radiation is given. The chemotherapy in this study includes the drug methotrexate. Read more about this study
- Who is it for?
- Ages Up to 5 years
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- Induction Chemotherapy, Low-Risk Therapy and High-Risk Therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 293 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 17 Dec 2007to Apr 2029
- Phase
- Phase 2
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 5 years
- All sexes
- No healthy volunteers
- Child
Histologically confirmed newly diagnosed CNS tumors of any of the following :
- Medulloblastoma (all histologic subtypes, including medullomyoblastoma and melanotic medulloblastoma)
- Supratentorial primitive neuroectodermal tumor (PNET) (including CNS neuroblastoma or ganglioneuroblastoma, medulloepithelioma, and ependymoblastoma)
- Pineoblastoma
- Atypical teratoid rhabdoid tumor (ATRT)
- Choroid plexus carcinoma
- High grade glioma (including anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic ganglioglioma, pleomorphic xanthoastrocytoma with anaplastic features, high-grade astroblastoma , anaplastic pilocytic astrocytoma, malignant glioneuronal tumor, glioblastoma multiforme), or gliosarcoma,
- Ependymoma (including all ependymoma histological variants)
- Age < 3 years at time of diagnosis for all histological diagnosis. Medulloblastoma patients ≥ 3 and < 5years old at diagnosis who have non-metastatic disease with no more than 1cm2 of residual tumor are also eligible.
- Meets criteria for 1 of the following risk groups:
- Low-risk group:
- Histologically confirmed nodular desmoplastic medulloblastoma, including medulloblastoma with extensive nodularity
- Focal areas of anaplasia or other atypical features suggesting more aggressive phenotype in a tumor otherwise considered nodular desmoplastic should be treated on the intermediate-risk group, with final risk stratification at the discretion of principal investigator and study pathologist
- No evidence of CNS metastasis 7 to 28 days after surgery by MRI and cytologic examination of lumbar cerebrospinal fluid (CSF)
- Ventricular CSF from a shunt or Ommaya reservoir may be used to rule out M1 disease when lumbar puncture is medically contraindicated
- Intermediate-risk group assignment when there is no other evidence of metastasis and CSF sampling is not possible
- Gross total resection, defined as residual tumor or imaging abnormality (not definitive for residual tumor) with a size of < 1 cm2 confirmed on postoperative CT scan or MRI
- Brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size < 1 cm2) and otherwise meets criteria for the low-risk group, the patient will be classified as low-risk
- Desmoplastic medulloblastoma patients who are ≥3 -<5 years of age will NOT be eligible for the low risk arm of the protocol.
- Intermediate-risk group:
- Histologically confirmed nodular desmoplastic medulloblastoma with less than gross total resection and no evidence of metastasis
- Any eligible histologic diagnosis other than desmoplastic medulloblastoma with no evidence of CNS metastasis
- Medulloblastoma patients who are ≥3 and < 5 yrs of age irrespective of histology and with no evidence of CNS metastasis
- High-risk group:
- Any eligible histologic diagnosis with evidence of CNS metastasis
- Patients with extraneural metastasis are eligible for treatment on the high-risk group
PATIENT CHARACTERISTICS:
- Lansky performance status ≥ 30 (except for posterior fossa syndrome)
- WBC > 2,000/mm3
- Platelets > 50,000/mm3 (without support)
- Hemoglobin > 8 g/dL (with or without support)
- ANC > 500/mm3
- Serum creatinine < 3 times upper limit of normal (ULN)
- ALT < 5 times ULN
- Total bilirubin < 3 times ULN
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No more than 31 days since prior definitive surgery
- No prior radiotherapy or chemotherapy other than corticosteroid therapy
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States5 sites
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Lucile Packard Children's Hospital at Stanford University Medical Center
Palo Alto, California, 94304
Children's Hospitals and Clinics of Minnesota - St. Paul
Saint Paul, Minnesota, 55102
Rady Children's Hospital
San Diego, California, 92123
Australia1 site
Lady Cilento Children's Hospital, Brisbane
Brisbane, Queensland, 4029
About this study
RATIONALE: In this study a combination of anti-cancer drugs (chemotherapy) is used to treat brain tumors in young children. Using chemotherapy gives the brain more time to develop before radiation is given. The chemotherapy in this study includes the drug methotrexate. This drug was an important part of the two clinical trials which resulted in the best survival results for children less than 3 years of age with medulloblastoma. Most patients treated on this trial will also receive radiation which is carefully targeted to the area of the tumor. This type of radiation (focal conformal or proton beam radiotherapy) may result in fewer problems with thinking and learning than radiation to the whole brain and spinal cord.
PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed central nervous system tumors.
Read the detailed description
All patients with medulloblastoma who were diagnosed prior to their 3rd birthday will contribute to both the biology and therapeutic primary objectives of this protocol. Furthermore patients who were ≥3 and <5 years old at the time of diagnosis will also be included in the cohort for these primary objectives as long as they meet the eligibility criteria as outlined in Amendment 8.0 of this protocol. Patients in the 3-5 year old age cohort who enrolled on previous versions of this protocol and who do not meet the criteria as outlined in Amendment 8.0 of this protocol will be excluded from the outcome analyses of the biology and therapeutic primary objectives of the protocol.
OBJECTIVES:
Primary
- To identify patterns of methylation profiling that are associated with progression-free survival among young pediatric patients with medulloblastoma treated with risk-adapted therapy.
- To estimate the event-free survival distribution of young medulloblastoma patients treated with risk-adapted therapy.
Secondary
- To perform high-resolution genome-wide analyses of chromosomal abnormalities and gene expression patterns, and evaluate the relationship of these to other clinicopathological variables.
- To evaluate specific tumor types for molecular abnormalities with suspected prognostic or therapeutic significance.
- To evaluate the feasibility of collecting frozen and fixed tumor samples for analysis using high-resolution molecular biology tools.
- To estimate the event-free and overall survival of patients treated with the proposed risk-adapted therapy regimen, and to descriptively compare these survival rates to historical controls.
- To estimate the rates of local and distant disease progression in patients treated with focal radiotherapy (RT) to the post-operative tumor bed using a 5 mm clinical target volume margin.
- To estimate the objective response rate (sustained for 8 weeks) to induction chemotherapy including high-dose intravenous methotrexate for patients with residual or metastatic disease.
- To evaluate the feasibility and toxicity of administering low-dose intravenous vinblastine in conjunction with induction chemotherapy to patients with metastatic disease.
- To evaluate the feasibility and toxicity of administering consolidation therapy including cyclophosphamide and pharmacokinetically targeted topotecan to patients with metastatic disease, and to estimate the sustained (for 8 weeks) objective response rate (complete response and partial response) to such therapy in patients with measurable residual disease after induction.
- To evaluate the feasibility and toxicity of administering oral maintenance therapy in young children.
- To use quantitative magnetic resonance (MR) measures (volumetric, diffusion, and perfusion) of young brain tumor patients receiving chemotherapy including high-dose intravenous methotrexate to assess impact of treatment on developing brain.
- To investigate the feasibility of using PET as an in-vivo dosimetric and distal edge verification system for patients treated with proton beam therapy (for participants enrolled at St Jude only).
OUTLINE: This is a multicenter study. Patients are stratified according to disease risk (low-risk vs intermediate-risk vs high-risk). Therapy consists of risk adapted induction, consolidation and maintenance chemotherapy. Focal irradiation is given to intermediate risk patients who have reached at least 12 months of age upon completion of induction. Intermediate risk patients who have not will receive low risk chemotherapy to delay RT until the age of 12 months.
Patients may consent to provide tumor tissue and blood samples for biological studies. Tumor tissues are analyzed for the activation of the wnt signaling pathway (β-catenin), activation of the shh signaling pathway (Gli-1/SFRP1), and ERBB2; validation of novel patterns of gene expression via immunohistochemical (IHC) analysis; loss of chromosomes 6, 8p, 9q22, isochromosome 17q; amplification of MYCC, MYCN, and MYCL; validation of genetic abnormalities via interphase fluorescence in situ hybridization (iFISH); construction of gene expression profiles via microarray analysis; single nucleotide polymorphism (SNP) analysis for DNA purity and integrity using UV spectrophotometry and agarose gel electrophoresis; amplification of DNA via PCR and a combination of previously published and 'in-house' generated primers; potential oncogenes and tumor suppressor genes via DNA sequence analysis; expression of a number of cell signal proteins implicated in the biology of medulloblastoma via western blot; expression of additional proteins encoded by genes associated through SNP and gene expression array analysis with clinical disease behavior; and differential expression pattern of genes detected using microarray analysis via RT-PCR. DNA extraction and construction of tissue microarrays (TMAs) from tumor tissue will also be used for future IHC and FISH analysis. Blood samples are analyzed for constitutional DNA from patients whose tumors contain gene mutations via sequence analysis of constitutional DNA; cyclophosphamide and its metabolites via liquid chromatography mass spectroscopy method; topotecan lactone via isocratic high-performance liquid chromatography assay with fluorescence detection; and alpha-1-acid glycoprotein (AAGP) concentrations via immunoturbidimetric assay.
After completion of study treatment, patients are followed every 6 months for 5 years.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- Induction Chemotherapy, Low-Risk Therapy, High-Risk Therapy, Intermediate-Risk Therapy
- Keywords
- untreated childhood medulloblastoma, untreated childhood supratentorial primitive neuroectodermal tumor, untreated childhood pineoblastoma, childhood atypical teratoid/rhabdoid tumor, childhood choroid plexus tumor, childhood high grade glioma, newly diagnosed childhood ependymoma
- Medical subject headings
- Central Nervous System Neoplasms, Rhabdoid Tumor, Choroid Plexus Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Induction ChemotherapyDrug
Also called MTX (methotrexate), Oncovin(R) (vincristine), Platinol-AQ(R) (cisplatin), Cytoxan(R) (cyclophosphamide)
All patients will receive 4 identical cycles of induction chemotherapy including highdose (5 g/m2 or 2.5g/m2 for patients less than or equal to 31 days of age at enrollment) intravenous methotrexate and standard dose vincristine, cisplatin, and cyclophosphamide.
Low-Risk TherapyDrug
Also called Cytoxan(R) (cyclophosphamide), Paraplatin(R) (carboplatin), Vepesid(R), VP-16 (etoposide), Hycamptin(R) (topotecan)
Induction will be followed by further conventional chemotherapy with carboplatin, cyclophosphamide, and etoposide. After consolidation, patients will receive 6 cycles of oral maintenance chemotherapy with cyclophosphamide, topotecan, and depending on the diagnosis, either erlotinib or etoposide (VP-16).
High-Risk TherapyDrug
Also called Velban(R) (vinblastine), Cytoxan(R) (cyclophosphamide), Hycamptin(R) (topotecan), Tarceva(TM) (erlotinib)
High risk patients will also receive vinblastine with each course of induction chemotherapy. Induction will be followed by either chemotherapy with targeted intravenous topotecan and cyclophosphamide or optional craniospinal irradiation (CSI). CSI will be offered only to patients who reach 3 years of age by the end of induction only. After consolidation, all patients will receive 6 cycles of oral maintenance chemotherapy with cyclophosphamide, topotecan, and depending on the diagnosis, either erlotinib or etoposide (VP-16).
Intermediate-Risk TherapyDrug
Also called Cytoxan(R) (cyclophosphamide), Hycamptin(R) (topotecan), Tarceva(TM) (erlotinib), Vepesid(R), VP-16 (etoposide)
Induction will be followed by consolidation focal radiotherapy (RT) to the tumor bed. Patients less than 12 months old upon completion of induction will receive low risk chemotherapy to delay RT until the age of 12 months. After consolidation, patients will receive 6 cycles of oral maintenance chemotherapy with cyclophosphamide, topotecan, and depending on the diagnosis, either erlotinib or etoposide (VP-16).
Note: The option to receive focal proton beam irradiation was suspended 10/29/2015. Focal photon beam irradiation continues as part of the treatment plan.
| Study group | Role | What they receive |
|---|---|---|
| Low-Risk Patients | Experimental | Patients with GTR/M0 medulloblastoma, nodular desmoplastic or high grade glioma histology will receive induction chemotherapy and low-risk therapy.
Note: Accrual to the low-risk medulloblastoma cohort is closed as of 12/2/2015. Accrual to the low-risk high grade glioma remains open. Receives: Drug: Induction Chemotherapy; Drug: Low-Risk Therapy |
| High-Risk Patients | Experimental | Patients with CNS metastatic disease will receive induction chemotherapy and high-risk therapy. Receives: Drug: Induction Chemotherapy; Drug: High-Risk Therapy |
| Intermediate-Risk Therapy | Experimental | Patients with M0 medulloblastoma or nodular desmoplastic histology with less than a GTR, other histologic diagnoses with no metastatic disease, will receive induction chemotherapy and intermediate-risk therapy. Receives: Drug: Induction Chemotherapy; Drug: Intermediate-Risk Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients
Progression was defined as 25% increase in the size of any measurable lesion; the appearance of a new lesion; or the conversion of negative cerebrospinal fluid (CSF) cytology to positive. Defined as the time interval from date on treatment until the date of first progression, medulloblastoma-related death or date of last contact for patients who have not experienced an event. All eligible medulloblastoma patients who received any methotrexate are included in this analysis.
Measured: From date on treatment until date of first progression or relapse or disease related death or date of last contact, estimated at 1 year after treatment
Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients by DNA Methylation Subgroup
Defined as the time interval from date on treatment until the date of first progression, medulloblastoma-related death or date of last contact for patients who have not experienced an event. Eligible medulloblastoma patients who received any methotrexate and had molecularly confirmed medulloblastoma are included in this analysis. Five patients were excluded as 3 had no archival tissue available and 2 were found to not be medulloblastoma by methylation profile.
Measured: From date on treatment to date of first progression or relapse or disease related death or date of last contact, estimated at 1 year after treatment
Percent Probability of Event-free Survival (EFS) for Medulloblastoma Patients
Defined as the time interval from date on treatment until the date of first progression, second malignancy or death due to any cause; or date of last contact for patients who have not experienced an event. All eligible medulloblastoma patients who received any methotrexate are included in this analysis.
Measured: From date on treatment to date of first progression, relapse, second malignancy or death from any cause or to date of last contact, estimated at 1 year after
Secondary outcomes (79)
Number of Participants With Chromosomal Abnormalities
Amplifications and deletions (gains and losses) for chromosomes of interest are shown in the table of measured values.
Measured: Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment
Numbers of Patients With Gene Alterations
Gene alterations, which include single nucleotide variants (SNPs), amplifications, deletions, translocations, indels, and germline alterations are shown for specific genes of interest in the results table.
Measured: Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment
Numbers of Patients With Molecular Abnormalities by Tumor Type
Alterations included single nucleotide variants (SNPs), amplifications, deletions, translocations, indels, and germline alterations. Cytogenetic information shows gains and losses as specified in the table of measured values.
Measured: Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment
Number of Successful Collections for Frozen and Fixed Tumor Samples
Successful collections will be defined as the number of patients who have frozen/fixed tumor samples available.
Measured: Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment
Event-free Survival (EFS) Compared to Historical Controls
EFS was measured from the date of initial treatment to the earliest date of disease progression, second malignancy or death for patients who fail; and to the date of last contact for patients who remain at risk for failure. 1-year EFS estimates are reported by risk group. EFS was compared to St. Jude historical cohorts by risk group using hazard ratios with 95% confidence intervals.
Measured: From date on treatment until date of first event (progression, second malignancy or death) or until date of last contact, assessed up to 10 years
Overall Survival (OS) Compared to Historical Controls
OS was measured from the date of initial treatment to date of death or to date of last contact for survivors. 1-year OS estimates were reported by risk group. OS was compared to St. Jude historical cohorts by risk group using hazard ratios with 95% confidence intervals.
Measured: 1 year after treatment initiation of last patient
Percentage of Patients With Objective Responses Rate to Induction Chemotherapy
For patients treated in the intermediate and high risk strata with residual or metastatic disease we will estimate the stratum-specific objective response rate (complete response (CR) or partial response [ PR]). All patients who receive at least 1 -dose of methotrexate are evaluable for response. Objective responses must be sustained for at least eight weeks.
Measured: From on-study date to 2 months after completion of induction chemotherapy (up to 4 months after on-study date)
Feasibility and Toxicity of Administering Vinblastine With Induction Chemotherapy for Patients With Metastatic Disease as Measured by the Percentage of Courses Delayed for More Than 7 Days Due to Toxicity
For the subset of patients with metastatic disease (high-risk group patients), during induction, the proportion percentage of courses during which subsequent chemotherapy administration was delayed for more than 7 days due to toxicity will be calculated. Patients were to receive 4 courses of induction and then consolidation chemotherapy.
Measured: From on-study date up to 4 months after on-study date
Feasibility and Toxicity of Administering Consolidation Therapy Including Cyclophosphamide and Pharmacokinetically Targeted Topotecan to Patients With Metastatic Disease Based on the Percentage of Courses Delayed for More Than 7 Days Due to Toxicity
For the subset of patients with metastatic disease (high-risk group patients), during consolidation, we will calculate the number and proportion of courses during which subsequent chemotherapy administration was delayed for more than 7 days due to toxicity. Patients were to received 2 courses of consolidation chemotherapy and then maintenance therapy.
Measured: At completion of consolidation therapy (up to 6 months after on-study date)
Percent of Patients With Sustained Objective Responses Rate After Consolidation
For patients enrolled on the high-risk arm with measurable residual disease after induction treated with consolidation therapy, we will estimate the objective response (complete response (CR)/partial response (PR)) rate after consolidation therapy with a 95% confidence interval. Objective responses must be sustained for at least eight weeks. All patients who receive at least 1 dose of cyclophosphamide or topotecan during consolidation are evaluable for response.
Measured: 8 weeks after completion of consolidation therapy (up to 8 months after on-study date)
Feasibility and Toxicity of Administering Oral Maintenance Therapy in Children <3 Years of Age as Measured by the Percentage of Total Scheduled Maintenance Doses Received
These data are based on patient diaries. For children <3 years of age, we will calculate the percentage of total scheduled doses each patient received per course for each of the oral maintenance courses and report the overall average number percentage of doses received per course across patients. If patients received all planned doses, their percentage would be 100%. If the average percentage was less than 75%, then feasibility would be in question.
Measured: From start of oral maintenance therapy (approximately 6 months after on-study date) to completion of oral maintenance therapy (up to 1 year after on-study date)
Percent of PET Scans With Loss of Signal Intensity
Measures will be analyzed for intermediate risk participants who receive proton beam therapy (PBT) and who consent. This objective aims to assess the feasibility of using post-proton beam therapy (PBT) positron emission tomography (PET) as an in-vivo dosimetric and distal edge verification system in this patient population. To quantify the decay in signal, 134 scans from 53 patients were analyzed by recording the mean activation value (MAV), the average recorded PET signal from activation, within the target volume. With each patient being given the same dose, the percent standard deviation in the MAV can serve as a quantitative representation of signal loss due to radioactive decay.
Measured: Up to 3 times during RT consolidation
Concentration of Cerebrospinal Fluid Neurotransmitters
Concentrations of various neurotransmitters in cerebrospinal fluid were measured at 5 timepoints. The median concentration of each neurotransmitter at each time point was calculated and provided with a full range.
Measured: Baseline, at the completion of therapy, and every 12 months up to 36 months after off therapy date
Number and Type of Genetic Polymorphisms
Types of genetic polymorphisms of neurotransmitters were examined. We studied 3 genetic polymorphisms; these were types of genetic polymorphisms involved in dopamine metabolism. They were as follows: rs6323, rs4680, and rs6280.
Measured: At study enrollment (Day 0)
Pharmacogenetic Variation on Central Nervous System Transmitters
Frequencies of genetic polymorphisms were reported.
Measured: At study enrollment (Day 0)
Number of Participants With Endocrinopathy
Endocrine screening and growth hormone (GH) testing were done in consenting intermediate risk patients at the end of induction therapy, the end of all therapy, and at 6, 12, 24, 36, 48, and 60 months off therapy. Endocrinopathy was defined as the presence of central hypothyroidism (free T4 concentration below normal with low or normal TSH concentration), growth hormone deficiency (peak growth hormone concentration below 5 ng/mL on dynamic testing), or ACTH deficiency (cortisol concentration below 14 ug/dL after low dose cosyntropin stimulation). Numbers of participants with endocrinopathy at each time point are reported. Please note the small numbers of participants with available data.
Measured: End of induction therapy (approximately 16 weeks from start of treatment), end of therapy (approximately 48 weeks from start of treatment), and 6, 12, 24, 36, 48, and 60 months off therapy
Growth Hormone Secretion
Growth hormone secretion was measured in consenting intermediate risk patients at the end of induction therapy, the end of all therapy, and at 6, 12, 24, 36, 48, and 60 months off therapy. Mean growth hormone secretion values are reported by assessment time point. Please note the small numbers of participants with available data.
Measured: End of induction therapy (approximately 16 weeks from start of treatment), end of therapy (approximately 48 weeks from start of treatment), and 6, 12, 24, 36, 48, and 60 months off therapy
Methotrexate Clearance in Induction Cycle 1
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis.
Measured: Pre-infusion and 6, 23, 42, 66 hours from start of Methotrexate (MTX)
Methotrexate Clearance in Induction Cycle 2
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis.
Measured: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Methotrexate Clearance in Induction Cycle 3
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis.
Measured: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Methotrexate Clearance in Induction Cycle 4
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis.
Measured: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Methotrexate Volume of Central Compartment in Induction Cycle 1
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis.
Measured: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Methotrexate Volume of Central Compartment in Induction Cycle 2
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis.
Measured: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Methotrexate Volume of Central Compartment in Induction Cycle 3
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis.
Measured: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Methotrexate AUC0-66h in Induction Cycle 1
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis.
Measured: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Methotrexate AUC0-66h in Induction Cycle 2
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis.
Measured: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Methotrexate Volume of Central Compartment in Induction Cycle 4
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis.
Measured: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Methotrexate AUC0-66h in Induction Cycle 3
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis.
Measured: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Methotrexate AUC0-66h in Induction Cycle 4
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis.
Measured: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 1
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis.
Measured: 42 hours from start of MTX
Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 2
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis.
Measured: 42 hours from start of MTX
Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 3
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis.
Measured: 42 hours from start of MTX
Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 4
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis.
Measured: 42 hours from start of MTX
Cyclophosphamide Clearance in Induction Chemotherapy
Cyclophosphamide plasma concentration-time data are collected on day 9 in one cycle of induction chemotherapy. Individual estimates of cyclophosphamide clearance are obtained using post hoc analysis.
Measured: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 1
Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of cyclophosphamide clearance are obtained using post hoc analysis.
Measured: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 2
Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of cyclophosphamide clearance are obtained using post hoc analysis.
Measured: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Cyclophosphamide Apparent Oral Clearance in Maintenance Chemotherapy Cycle A1
Cyclophosphamide plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of cyclophosphamide apparent oral clearance are obtained using post hoc analysis.
Measured: Pre-dose, 0.5, 1.75, 3 and 6 hours post-dose
Cyclophosphamide AUC0-24h in Induction Chemotherapy
Cyclophosphamide plasma concentration-time data are collected on day 9 in one cycle of induction chemotherapy. Individual estimates of cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Measured: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1
Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Measured: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1
4-OH cyclophosphamide plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Measured: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2
Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Measured: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1
Cyclophosphamide plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of cyclophosphamide AUC0-24h are obtained using post hoc analysis.
Measured: Pre-dose, 0.5, 1.75, 3, 6, and 24 hours post-dose
4-OH Cyclophosphamide AUC0-24h in Induction Chemotherapy
4-OH cyclophosphamide plasma concentration-time data are collected on day 9 in one cycle of induction chemotherapy. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Measured: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2
4-OH cyclophosphamide plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Measured: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
4-OH Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1
4-OH cyclophosphamide plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Measured: Pre-dose, 0.5, 1.75, 3, 6, and 24 hours post-dose
CEPM AUC0-24h in Induction Chemotherapy
Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected on day 9 in one induction cycle. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Measured: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
CEPM AUC0-24h in Consolidation Chemotherapy Cycle 1
Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Measured: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
CEPM AUC0-24h in Consolidation Chemotherapy Cycle 2
Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Measured: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
CEPM AUC0-24h in Maintenance Chemotherapy Cycle A1
Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Measured: Pre-dose, 0.5, 1.75, 3, 6, and 24 hours post-dose
Participants With Empirical Dosage Achieving Target System Exposure of Intravenous Topotecan
Number of participants who successfully achieve target systemic exposure of intravenous topotecan after an empiric dosage during consolidation phase of therapy are reported.
Measured: Pre-infusion, 5 min., 1, and 3 hours from end of infusion
Participants With PK-guided Dosage Adjustment Achieving Target System Exposure of Intravenous Topotecan
Number of participants who successfully achieve target systemic exposure of intravenous topotecan after a pharmacokinetic-guided dosage adjustment during consolidation phase of therapy are reported.
Measured: Pre-infusion, 5 min., 1, and 3 hours from end of infusion
Topotecan Clearance in Consolidation Chemotherapy
Topotecan plasma concentration-time data are collected on day 1 of consolidation cycle 1 after a single IV dose. Individual estimates of topotecan clearance are obtained using post hoc analysis.
Measured: Pre-infusion, 5 min., 1, and 3 hours from end of infusion
Topotecan Apparent Oral Clearance in Maintenance Chemotherapy
Topotecan plasma concentration-time data are collected on day 1 of maintenance cycle A1 after a single oral dose. Individual estimates of topotecan apparent oral clearance are obtained using post hoc analysis.
Measured: Pre-dose, 0.25, 1.5 and 6 hours post-dose
Topotecan AUC0-24h in Consolidation Chemotherapy
Topotecan plasma concentration-time data are collected on day 1 of consolidation cycle 1 after a single IV dose. Individual estimates of topotecan AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Measured: Pre-infusion, 5 min., 1, 3, and 24 hours from end of infusion
Topotecan AUC0-24h in Maintenance Chemotherapy
Topotecan plasma concentration-time data are collected on day 1 of maintenance cycle A1 after a single oral dose. Individual estimates of topotecan AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Measured: Pre-dose, 0.25, 1.5, 6, and 24 hours post-dose
Erlotinib Apparent Oral Clearance
Erlotinib plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of erlotinib apparent oral clearance are obtained using post hoc analysis.
Measured: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose
Erlotinib Apparent Volume of Central Compartment
Erlotinib plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of erlotinib apparent volume of central compartment are obtained using post hoc analysis.
Measured: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose
Erlotinib AUC0-24h
Erlotinib plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of erlotinib AUC0-24h (area under concentration curve from 0 to 24 hours post-dose) are obtained using post hoc analysis.
Measured: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose
OSI-420 AUC0-24h
Erlotinib metabolite OSI-420 plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of OSI-420 AUC0-24h (area under concentration curve from 0 to 24 hours post-dose) are obtained using post hoc analysis.
Measured: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose
Rate of Local Disease Progression
Local failure was defined as the interval from end of RT to date of local failure (or combined local + distant failure). Competing events were distant failure or second malignancy. Patients without an event were censored at date of last contact. The 1-year cumulative incidence was estimated and reported with a 95% confidence interval.
Measured: 1 year after completion of radiation therapy for last patient
Rate of Distant Disease Progression
Distant failure was defined as the interval from end of RT to date of distant failure (or combined local + distant failure). Competing events were local failure or second malignancy. Patients without an event were censored at date of last contact. The 1-year cumulative incidence was estimated and reported with a 95% confidence interval.
Measured: 1 year after completion of radiation therapy for last patient
Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores
Global cognitive functioning was measured based on Cognitive Composite Scores from the Bayley III instrument for subjects <3 years of age and on estimated IQ scores from the Stanford Binet V instrument for subjects ≥3 years of age. Higher scores indicate better performance. The normative mean is 100 with a standard deviation of 15.
Measured: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy
Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores
Scores measuring attention were obtained from the Attention Problems T-score on the BASC-2 instrument which is a parent report. Higher scores indicate more attention problems. The normative mean is 50 with a standard deviation of 10.
Measured: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy
Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores
Scores measuring processing speed were obtained based on the visual matching standard score from the Woodcock Johnson III instrument. Higher scores indicate better performance. The normative mean is 100 with a standard deviation of 15.
Measured: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy
Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores
Scores measuring executive functioning were obtained from Global Executive Composite (GEC) T-scores, which were obtained from the Behavior Rating Inventory of Executive Function (BRIEF) instrument which is a parent report. Higher scores indicate more problems. The normative mean is 50 with a standard deviation of 10.
Measured: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy
Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores
Scores measuring working memory were obtained from Working Memory T-scores, which were obtained from the Behavior Rating Inventory of Executive Function (BRIEF) instrument which is a parent report. Higher scores indicate more problems. The normative mean is 50 with a standard deviation of 10.
Measured: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy
Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores
Scores measuring verbal fluency were obtained from Retrieval Fluency standard scores on the Woodcock Johnson III instrument. Higher scores indicate better performance. The normative mean is 100 with a standard deviation of 15.
Measured: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores
Scores measuring visual-spatial reasoning were obtained from VMI T-scores on the Beery VMI instrument. Higher scores indicate better performance. The normative mean is 50 with standard deviation of 10.
Measured: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores
Scores measuring visual-spatial reasoning were obtained from Visual Perception T-scores on the Beery Visual Motor Integration (VMI) instrument. Higher scores indicate better performance. The normative mean is 50 with a standard deviation of 10.
Measured: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy
Change in Neurostructure, Especially White Matter Volume and Integrity
Quantitative MRI measures Fractional Anisotropy (FA) change per month in right frontal-lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy.
Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Measured: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Change in Neurostructure, Especially White Matter Volume and Integrity
Quantitative MRI measures Fractional Anisotropy (FA) change per month in left frontal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy.
Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Measured: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Change in Neurostructure, Especially White Matter Volume and Integrity
Quantitative MRI measures Fractional Anisotropy (FA) change per month in right parietal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy.
Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Measured: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Change in Neurostructure, Especially White Matter Volume and Integrity
Quantitative MRI measures Fractional Anisotropy (FA) change per month in left parietal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy.
Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Measured: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Change in Neurostructure, Especially White Matter Volume and Integrity
Quantitative MRI measures Fractional Anisotropy (FA) change per month in right occipital lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy.
Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Measured: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Change in Neurostructure, Especially White Matter Volume and Integrity
Quantitative MRI measures Fractional Anisotropy (FA) change per month in left occipital lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy.
Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Measured: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Change in Neurostructure, Especially White Matter Volume and Integrity
Quantitative MRI measures Fractional Anisotropy (FA) change per month in right temporal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy.
Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Measured: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Change in Neurostructure, Especially White Matter Volume and Integrity
Quantitative MRI measures Fractional Anisotropy (FA) change per month in left temporal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy.
Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Measured: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Change in Quantitative Magnetic Resonance (MR) Measures in the Frontal Lobe
Quantitative MRI measures Fractional Anisotropy (FA) change per month in frontal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy.
Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Measured: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Change in Quantitative MR Measures in the Right Frontal-parietal Regions
Quantitative MRI measures Fractional Anisotropy (FA) change per month in right frontal-parietal region over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy.
Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Measured: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2008 (estimated)
- Study start17 Dec 2007
- Primary completion27 Sep 2017
- Study completionApr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 293 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Florida, National Cancer Institute (NCI), The Pew Charitable Trusts
- Responsible party
- Sponsor
- Investigators
- Amar Gajjar, MD, Study chair, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00602667
- Sponsor's protocol ID
- SJYC07
- Other IDs
- R01CA154619, NCI-2011-01193
- Status last verified
- Oct 2026
- First submitted
- 10 Jan 2008
- Last updated
- 16 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Ali JS, Ashford JM, Swain MA, Harder LL, Carlson-Green BL, Miller JM, Wallace J, Kaner RJ, Billups CA, Onar-Thomas A, Merchant TE, Gajjar A, Conklin HM. Predictors of Cognitive Performance Among Infants Treated for Brain Tumors: Findings From a Multisite, Prospective, Longitudinal Trial. J Clin Oncol. 2021 Jul 20;39(21):2350-2358. doi: 10.1200/JCO.20.01687. Epub 2021 May 4.
PubMed 33945291Kumar R, Smith KS, Deng M, Terhune C, Robinson GW, Orr BA, Liu APY, Lin T, Billups CA, Chintagumpala M, Bowers DC, Hassall TE, Hansford JR, Khuong-Quang DA, Crawford JR, Bendel AE, Gururangan S, Schroeder K, Bouffet E, Bartels U, Fisher MJ, Cohn R, Partap S, Kellie SJ, McCowage G, Paulino AC, Rutkowski S, Fleischhack G, Dhall G, Klesse LJ, Leary S, Nazarian J, Kool M, Wesseling P, Ryzhova M, Zheludkova O, Golanov AV, McLendon RE, Packer RJ, Dunham C, Hukin J, Fouladi M, Faria CC, Pimentel J, Walter AW, Jabado N, Cho YJ, Perreault S, Croul SE, Zapotocky M, Hawkins C, Tabori U, Taylor MD, Pfister SM, Klimo P Jr, Boop FA, Ellison DW, Merchant TE, Onar-Thomas A, Korshunov A, Jones DTW, Gajjar A, Ramaswamy V, Northcott PA. Clinical Outcomes and Patient-Matched Molecular Composition of Relapsed Medulloblastoma. J Clin Oncol. 2021 Mar 1;39(7):807-821. doi: 10.1200/JCO.20.01359. Epub 2021 Jan 27.
PubMed 33502920Robinson GW, Rudneva VA, Buchhalter I, Billups CA, Waszak SM, Smith KS, Bowers DC, Bendel A, Fisher PG, Partap S, Crawford JR, Hassall T, Indelicato DJ, Boop F, Klimo P, Sabin ND, Patay Z, Merchant TE, Stewart CF, Orr BA, Korbel JO, Jones DTW, Sharma T, Lichter P, Kool M, Korshunov A, Pfister SM, Gilbertson RJ, Sanders RP, Onar-Thomas A, Ellison DW, Gajjar A, Northcott PA. Risk-adapted therapy for young children with medulloblastoma (SJYC07): therapeutic and molecular outcomes from a multicentre, phase 2 trial. Lancet Oncol. 2018 Jun;19(6):768-784. doi: 10.1016/S1470-2045(18)30204-3. Epub 2018 May 16.
PubMed 29778738