Brain and Central Nervous System TumorsPhase 3NCT00085202
Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor
A Phase 3 study testing filgrastim, cisplatin and cyclophosphamide in people with Brain and Central Nervous System Tumors, run by St. Jude Children's Research Hospital at 9 sites in 3 countries.
Trial summary
Drugs used in chemotherapy, such as vincristine, cisplatin, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. Read more about this study
- Who is it for?
- Ages 3 to 21 years
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- filgrastim, cisplatin and cyclophosphamide
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 416 participants
- Where
- 9 sitesin 3 countries
- Study dates
- Aug 2003to 31 Dec 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 3 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
DISEASE CHARACTERISTICS:
- Histologically confirmed diagnosis of 1 of the following:
- Medulloblastoma
- Supratentorial primitive neuroectodermal tumor (PNET)
- PNET variants (ependymoblastoma, pineoblastoma, CNS neuroblastoma)
- Atypical teratoid rhabdoid tumor (ATRT)
- Definitive surgery for CNS tumor within the past 31 days
- Meets one of the following risk criteria:
- Average-risk disease
- Localized disease with no overt evidence of invasion beyond the posterior fossa (or supratentorial compartment for PNET or ATRT) by intraoperative observations of the neurosurgeon AND postoperative CT scan or MRI
- T4 disease eligible if all of the following are true:
- Gross total resection determined by intraoperative observations of the neurosurgeon AND postoperative CT scan or MRI
- Residual tumor or imaging abnormality whose size is < 1.5 cm^2
- No evidence of CNS or extraneural metastasis by MRI of the spine (with and without contrast agent) or CT-based myelogram AND by cytologic examination of the lumbar cerebral spinal fluid (CSF) 14-28 days after surgery
- Brain stem invasion allowed in the absence of residual tumor (tumor < 1.5 cm^2 by imaging)
- High-risk disease meeting one of the following criteria:
- Metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination by imaging and/or cytologic examination of CSF)
- Presence of residual disease > 1.5 cm^2 at the primary site after surgery
PATIENT CHARACTERISTICS:
Age
- 3 to 21 at diagnosis
Performance status
- Lansky 30-100% (< 10 years old)
- Karnofsky 30-100% (≥ 10 years old) (except for posterior fossa syndrome)
Life expectancy
- Not specified
Hematopoietic
- Hemoglobin > 8 g/dL
- WBC > 2,000/mm^3
- Absolute neutrophil count > 500/mm^3
- Platelet count > 50,000/mm^3
Hepatic
- ALT < 5 times normal
- Bilirubin < 3.0 mg/dL
Renal
- Creatinine < 2.0 mg/dL OR
- Creatinine clearance > 70 mL/min
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- No prior chemotherapy
Endocrine therapy
- Prior corticosteroid therapy allowed
Radiotherapy
- No prior radiotherapy
Surgery
- See Disease Characteristics
Trial locations and contacts
9 sites in 3 countries.
9 sites in 3 countries
United States4 sites
Duke Comprehensive Cancer Center
Durham, North Carolina, 27710
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, 77030-2399
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Australia4 sites
Lady Cilento Children's Hospital, Brisbane
Brisbane, Queensland, 4029
Royal Children's Hospital
Parkville, Victoria, 3052
Sydney Children's Hospital
Randwick, New South Wales, 2031
Children's Hospital at Westmead
Westmead, New South Wales, 2145
About this study
Drugs used in chemotherapy, such as vincristine, cisplatin, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. Autologous stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy or radiation therapy. It is not yet known which radiation therapy regimen combined with chemotherapy and donor stem cell transplant is more effective in treating medulloblastoma, supratentorial primitive neuroectodermal tumor, or atypical teratoid rhabdoid tumor.
This phase III trial is studying two different regimens of radiation therapy when given together with chemotherapy and autologous stem cell transplant to see how well they work in treating patients with newly diagnosed medulloblastoma, supratentorial primitive neuroectodermal tumor, or atypical teratoid rhabdoid tumor.
Read more
PRIMARY OBJECTIVE:
- To assess the relationship between ERBB2 protein expression in tumors and progression-free survival probability for patients with medulloblastoma.
- To estimate the frequency of mutations associated with SHH and WNT tumors (as defined by gene expression profiling) via targeted sequencing performed in an independent cohort of WNT and SHH tumors (also defined by gene expression profiling).
Read the detailed description
SECONDARY OBJECTIVES:
- To compare the effects of a computer-based training system specifically targeting language, reading, and learning skills (Fast ForWord, Scientific Learning Corporation) with the current standard of care on reading decoding skills as measured by individual academic testing.
- To monitor for treatment failure in the posterior fossa of patients whose tumor bed receives a reduced volume of radiation.
- To correlate radiation dosimetry of target and normal tissues with rate and patterns of failure and longitudinal measures of audiometric, endocrine and cognitive effects.
EXPLORATORY OBJECTIVES:
- To estimate the change in neuropsychological performance from the neuropsychology assessment battery (intellect, academic achievement and cognitive ability) and examine the relationship of these changes to risk group, age at diagnosis, and parent measures.
- To evaluate the differences between neurotoxicity in the average-risk patient group with that in the high-risk group through qMRI, and fMRI.
- To develop or refine novel models relating impact of medulloblastoma therapy on neurocognitive performance to quantitative and functional neuroimaging measures.
OUTLINE: This is a multicenter study. Patients are stratified according to disease risk (high-risk disease vs average-risk disease).
Patients in both strata undergo peripheral blood stem cell or bone marrow harvest.
- Stratum 1 (high-risk group):
- Radiotherapy: Patients undergo craniospinal radiotherapy once daily 5 days a week for 6 weeks.
- High-dose chemotherapy and autologous stem cell transplantation (SCT): Six weeks after the completion of radiotherapy, patients receive high-dose chemotherapy comprising vincristine IV followed by cisplatin IV over 6 hours on day -4 and cyclophosphamide IV over 1 hour on days -3 and -2. Patients undergo autologous SCT on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover. Patients receive vincristine IV on day 6. High-dose chemotherapy and autologous SCT repeat every 4 weeks for 3 additional courses in the absence of unacceptable toxicity.
- Stratum 2 (average-risk group):
- Radiotherapy: Patients undergo craniospinal radiotherapy as in stratum 1, but at a lower dose.
- High-dose chemotherapy and autologous SCT: Patients receive high-dose chemotherapy, autologous SCT, G-CSF, and post-transplantation vincristine as in stratum 1.
Some patients undergo a neuropsychology assessment at baseline, before chemotherapy, and then annually for 5 years.
After completion of study therapy, patients are followed every 3 months until month 30 (2.5 years) after diagnosis and then every 6 months until month 72 (6 years) after diagnosis.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- filgrastim, cisplatin, cyclophosphamide, vincristine, autologous hematopoietic stem cell transplantation
- Keywords
- untreated childhood medulloblastoma, untreated childhood supratentorial primitive neuroectodermal tumor, childhood atypical teratoid/rhabdoid tumor, untreated childhood pineoblastoma
- Medical subject headings
- Central Nervous System Neoplasms, Rhabdoid Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgrastimBiological
Also called Neupogen(R), G-CSF
Given subcutaneously
cisplatinDrug
Also called Platinol-AQ(R)
Given IV
cyclophosphamideDrug
Also called Cytoxan(R)
Given IV
vincristineDrug
Also called Oncovin(R)
Given IV
autologous hematopoietic stem cell transplantationProcedure or surgery
Also called autologous HSCT
Patients undergo autologous stem cell transplantation
radiation therapyRadiation
Also called RT, Craniospinal radiotherapy
Patients undergo craniospinal radiotherapy once daily 5 days a week for 6 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Stratum 1 (high-risk group) | Experimental | Patients undergo craniospinal radiotherapy once daily 5 days a week for 6 weeks. Six weeks after the completion of radiotherapy, patients receive high-dose chemotherapy followed by autologous stem cell transplantation (SCT) and filgrastim (G-CSF) with post-transplantation vincristine. High-dose chemotherapy and autologous SCT repeat every 4 weeks for 3 additional courses in the absence of unacceptable toxicity.
Interventions: vincristine, cisplatin, cyclophosphamide, autologous hematopoietic stem cell transplantation, filgrastim, radiation therapy Receives: Biological: filgrastim; Drug: cisplatin; Drug: cyclophosphamide; Drug: vincristine; Procedure: autologous hematopoietic stem cell transplantation; Radiation: radiation therapy |
| Stratum 2 (average-risk group) | Experimental | Patients undergo craniospinal radiotherapy as in stratum 1, but at a lower dose. Patients receive high-dose chemotherapy, autologous SCT, G-CSF, and post-transplantation vincristine as in stratum 1.
Interventions: vincristine, cisplatin, cyclophosphamide, autologous hematopoietic stem cell transplantation, filgrastim, radiation therapy Receives: Biological: filgrastim; Drug: cisplatin; Drug: cyclophosphamide; Drug: vincristine; Procedure: autologous hematopoietic stem cell transplantation; Radiation: radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS) in ERBB2-Negative Tumors Compared to ERBB2-Positive Tumors
The relationship between ERBB2 protein expression in tumors and progression-free survival was assessed in 122 participants with a diagnosis of medulloblastoma and with ERBB2 protein assessments. If the ERBB2 value was greater than zero, the ERBB2 was defined as positive for the participant. If the ERBB2 value was zero, the ERBB2 was defined as negative. Progression-free survival was calculated from the date of diagnosis to the date of disease progression/relapse, the date of death, or the date of last contact. The log-rank test was used to compare the PFS distributions of ERBB2 groups.
Measured: 2 years after tumor cell analysis in 122 participants
Progression-Free Survival (PFS) Compared Between ERBB2 Assessment and Risk Group.
122 participants with a diagnosis of medulloblastoma were grouped by ERBB2 positive/negative assessment and risk group into 4 groups. Progression-free survival was calculated from the date of diagnosis to the date of disease progression/relapse, the date of death, or the date of last contact. The log-rank test was used to compare the PFS distributions of ERBB2 groups.
Measured: 2 years after tumor cell analysis in 122 participants
Frequency of Mutations Associated With SHH and WNT Tumors
The frequency of mutations for the main genes associated with SHH and WNT tumors identified via targeted sequencing based on formalin fixed paraffin embedded material is provided.
Measured: within 3.5 years following completion of accrual
Secondary outcomes (8)
Reading Decoding Composite Scores in the Intervention and Standard of Care Groups
SOC is standard-of-Care control group. Patients randomly assigned to the control group received the current standard of care. RI is Reading Intervention Group. Patients randomly assigned to Reading Intervention Group which is with The Fast ForWord program. Assessment of reading decoding was completed using the Woodcock Johnson, Third Edition (WJIII) Tests of Achievement (Woodcock, McGraw, \& Mather, 2001), with particular attention given to the reading and reading-related abilities. Two subtests were completed: (1) Letter-Word Identification, and (2) Word Attack, a test requiring the patient to read phonologically regular nonwords. The combination of these two subtests provided a standardized composite score of overall reading decoding ability with a population mean of 100 and a standard deviation of 15. Scores of 90-110 are considered to be in the average range, while those 80-89 are considered low-average (refer: Journal of Pediatric Psychology 39(4) pp. 450-458, 2014).
Measured: 5 years postdiagnosis
Number of Average Risk Patients Whose Treatment Failure Included the Posterior Fossa
To monitor for treatment failure in the posterior fossa of patients whose tumor bed receives a reduced volume of radiation.
Measured: Annually for 6 years post irradiation
Associative Memory for Two Risk Group at Enrollment
Assessment of associative memory at enrollment. Associate memory score is a representative measurement of learning and recalling pictograph representations of words. It measures associative memory (Long-Term Retrieval). Mean=100, SD=15, Average Range 85-115. Higher is better.
Measured: At enrollment
Associative Memory for Two Risk Group at 5 Years After Enrollment
Assessment of associative memory at 5 years after enrollment. Assessment of associative memory score at enrollment. Associate memory score is a representative measurement of learning and recalling pictograph representations of words. It measures associative memory (Long-Term Retrieval). Mean=100, SD=15, Average Range 85-115. Higher is better.
Measured: At 5 years after enrollment
Processing Speed for Two Risk Group at Enrollment
Assessment of Processing Speed at enrollment. This score measure of Processing Speed based on Visual Matching and Decision Speed tests. Mean=100, SD=15, Average Range 85-115. Higher is better.
Measured: At enrollment
Processing Speed for Two Risk Group at 5 Years After Enrollment
Assessment of Processing Speed at 5 years after enrollment. This score measure of Processing Speed based on Visual Matching and Decision Speed tests. Mean=100, SD=15, Average Range 85-115. Higher is better.
Measured: At 5 years after enrollment
Perceptual Speed for Two Risk Group at Enrollment
Assessment of Perceptual Speed at enrollment. It measures rapidly locating and circling identical numbers from a set of numbers which reflects perceptual speed. Mean=100, SD=15, Average Range 85-115. Higher is better.
Measured: At enrollment
Perceptual Speed for Two Risk Group at 5 Years After Enrollment
Assessment of Perceptual Speed at 5 years after enrollment. It measures rapidly locating and circling identical numbers from a set of numbers which reflects perceptual speed. Mean=100, SD=15, Average Range 85-115. Higher is better.
Measured: At 5 years after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2004 (estimated)
- Study startAug 2003
- Primary completionDec 2016
- Study completion31 Dec 2023
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 (5)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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 416 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Amar Gajjar, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00085202
- Sponsor's protocol ID
- SJMB03
- Other IDs
- NCI-2011-01185
- Status last verified
- Jan 2024
- First submitted
- 10 Jun 2004
- Last updated
- 8 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Acharya S, Guo Y, Patni T, Li Y, Wang C, Gargone M, Ashford JM, Wilson L, Faught A, Reddick WE, Patay Z, Gajjar A, Conklin HM, Merchant TE. Association Between Brain Substructure Dose and Cognitive Outcomes in Children With Medulloblastoma Treated on SJMB03: A Step Toward Substructure-Informed Planning. J Clin Oncol. 2022 Jan 1;40(1):83-95. doi: 10.1200/JCO.21.01480. Epub 2021 Oct 29.
PubMed 34714708Partanen M, Anghelescu DL, Hall L, Schreiber JE, Rossi M, Gajjar A, Jacola LM. Longitudinal associations between exposure to anesthesia and neurocognitive functioning in pediatric medulloblastoma. Eur J Cancer. 2021 May;148:103-111. doi: 10.1016/j.ejca.2021.02.010. Epub 2021 Mar 17.
PubMed 33743477Kumar 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 33502920Gajjar A, Robinson GW, Smith KS, Lin T, Merchant TE, Chintagumpala M, Mahajan A, Su J, Bouffet E, Bartels U, Schechter T, Hassall T, Robertson T, Nicholls W, Gururangan S, Schroeder K, Sullivan M, Wheeler G, Hansford JR, Kellie SJ, McCowage G, Cohn R, Fisher MJ, Krasin MJ, Stewart CF, Broniscer A, Buchhalter I, Tatevossian RG, Orr BA, Neale G, Klimo P Jr, Boop F, Srinivasan A, Pfister SM, Gilbertson RJ, Onar-Thomas A, Ellison DW, Northcott PA. Outcomes by Clinical and Molecular Features in Children With Medulloblastoma Treated With Risk-Adapted Therapy: Results of an International Phase III Trial (SJMB03). J Clin Oncol. 2021 Mar 1;39(7):822-835. doi: 10.1200/JCO.20.01372. Epub 2021 Jan 6.
PubMed 33405951Xu H, Robinson GW, Huang J, Lim JY, Zhang H, Bass JK, Broniscer A, Chintagumpala M, Bartels U, Gururangan S, Hassall T, Fisher M, Cohn R, Yamashita T, Teitz T, Zuo J, Onar-Thomas A, Gajjar A, Stewart CF, Yang JJ. Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss. Nat Genet. 2015 Mar;47(3):263-6. doi: 10.1038/ng.3217. Epub 2015 Feb 9.
PubMed 25665007
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor
- ClinicalTrials.gov ID
- NCT00085202
- Acronym / sponsor ID
- SJMB03
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- untreated childhood medulloblastoma, untreated childhood supratentorial primitive neuroectodermal tumor, childhood atypical teratoid/rhabdoid tumor, untreated childhood pineoblastoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 416 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Study start
- Aug 2003
- Primary completion
- Dec 2016 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 11 Jun 2004 (estimated)
- Results
- Posted 27 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Drugs used in chemotherapy, such as vincristine, cisplatin, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. Autologous stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy or radiation therapy. It is not yet known which radiation therapy regimen combined with chemotherapy and donor stem cell transplant is more effective in treating medulloblastoma, supratentorial primitive neuroectodermal tumor, or atypical teratoid rhabdoid tumor.
This phase III trial is studying two different regimens of radiation therapy when given together with chemotherapy and autologous stem cell transplant to see how well they work in treating patients with newly diagnosed medulloblastoma, supratentorial primitive neuroectodermal tumor, or atypical teratoid rhabdoid tumor.
PRIMARY OBJECTIVE:
- To assess the relationship between ERBB2 protein expression in tumors and progression-free survival probability for patients with medulloblastoma.
- To estimate the frequency of mutations associated with SHH and WNT tumors (as defined by gene expression profiling) via targeted sequencing performed in an independent cohort of WNT and SHH tumors (also defined by gene expression profiling).
Detailed description
SECONDARY OBJECTIVES:
- To compare the effects of a computer-based training system specifically targeting language, reading, and learning skills (Fast ForWord, Scientific Learning Corporation) with the current standard of care on reading decoding skills as measured by individual academic testing.
- To monitor for treatment failure in the posterior fossa of patients whose tumor bed receives a reduced volume of radiation.
- To correlate radiation dosimetry of target and normal tissues with rate and patterns of failure and longitudinal measures of audiometric, endocrine and cognitive effects.
EXPLORATORY OBJECTIVES:
- To estimate the change in neuropsychological performance from the neuropsychology assessment battery (intellect, academic achievement and cognitive ability) and examine the relationship of these changes to risk group, age at diagnosis, and parent measures.
- To evaluate the differences between neurotoxicity in the average-risk patient group with that in the high-risk group through qMRI, and fMRI.
- To develop or refine novel models relating impact of medulloblastoma therapy on neurocognitive performance to quantitative and functional neuroimaging measures.
OUTLINE: This is a multicenter study. Patients are stratified according to disease risk (high-risk disease vs average-risk disease).
Patients in both strata undergo peripheral blood stem cell or bone marrow harvest.
- Stratum 1 (high-risk group):
- Radiotherapy: Patients undergo craniospinal radiotherapy once daily 5 days a week for 6 weeks.
- High-dose chemotherapy and autologous stem cell transplantation (SCT): Six weeks after the completion of radiotherapy, patients receive high-dose chemotherapy comprising vincristine IV followed by cisplatin IV over 6 hours on day -4 and cyclophosphamide IV over 1 hour on days -3 and -2. Patients undergo autologous SCT on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover. Patients receive vincristine IV on day 6. High-dose chemotherapy and autologous SCT repeat every 4 weeks for 3 additional courses in the absence of unacceptable toxicity.
- Stratum 2 (average-risk group):
- Radiotherapy: Patients undergo craniospinal radiotherapy as in stratum 1, but at a lower dose.
- High-dose chemotherapy and autologous SCT: Patients receive high-dose chemotherapy, autologous SCT, G-CSF, and post-transplantation vincristine as in stratum 1.
Some patients undergo a neuropsychology assessment at baseline, before chemotherapy, and then annually for 5 years.
After completion of study therapy, patients are followed every 3 months until month 30 (2.5 years) after diagnosis and then every 6 months until month 72 (6 years) after diagnosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stratum 1 (high-risk group) | Experimental | Biological: filgrastim, Drug: cisplatin, Drug: cyclophosphamide, Drug: vincristine, Procedure: autologous hematopoietic stem cell transplantation, Radiation: radiation therapyPatients undergo craniospinal radiotherapy once daily 5 days a week for 6 weeks. Six weeks after the completion of radiotherapy, patients receive high-dose chemotherapy followed by autologous stem cell transplantation (SCT) and filgrastim (G-CSF) with post-transplantation vincristine. High-dose chemotherapy and autologous SCT repeat every 4 weeks for 3 additional courses in the absence of unacceptable toxicity. Interventions: vincristine, cisplatin, cyclophosphamide, autologous hematopoietic stem cell transplantation, filgrastim, radiation therapy |
| Stratum 2 (average-risk group) | Experimental | Biological: filgrastim, Drug: cisplatin, Drug: cyclophosphamide, Drug: vincristine, Procedure: autologous hematopoietic stem cell transplantation, Radiation: radiation therapyPatients undergo craniospinal radiotherapy as in stratum 1, but at a lower dose. Patients receive high-dose chemotherapy, autologous SCT, G-CSF, and post-transplantation vincristine as in stratum 1. Interventions: vincristine, cisplatin, cyclophosphamide, autologous hematopoietic stem cell transplantation, filgrastim, radiation therapy |
Who may qualify
- Ages
- 3 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| filgrastimAlso: Neupogen(R), G-CSFGiven subcutaneously | Biological | Stratum 1 (high-risk group), Stratum 2 (average-risk group) |
| cisplatinAlso: Platinol-AQ(R)Given IV | Drug | Stratum 1 (high-risk group), Stratum 2 (average-risk group) |
| cyclophosphamideAlso: Cytoxan(R)Given IV | Drug | Stratum 1 (high-risk group), Stratum 2 (average-risk group) |
| vincristineAlso: Oncovin(R)Given IV | Drug | Stratum 1 (high-risk group), Stratum 2 (average-risk group) |
| autologous hematopoietic stem cell transplantationAlso: autologous HSCTPatients undergo autologous stem cell transplantation | Procedure or surgery | Stratum 1 (high-risk group), Stratum 2 (average-risk group) |
| radiation therapyAlso: RT, Craniospinal radiotherapyPatients undergo craniospinal radiotherapy once daily 5 days a week for 6 weeks. | Radiation | Stratum 1 (high-risk group), Stratum 2 (average-risk group) |
Primary outcome
Progression-Free Survival (PFS) in ERBB2-Negative Tumors Compared to ERBB2-Positive Tumors
Time frame: 2 years after tumor cell analysis in 122 participants
The relationship between ERBB2 protein expression in tumors and progression-free survival was assessed in 122 participants with a diagnosis of medulloblastoma and with ERBB2 protein assessments. If the ERBB2 value was greater than zero, the ERBB2 was defined as positive for the participant. If the ERBB2 value was zero, the ERBB2 was defined as negative. Progression-free survival was calculated from the date of diagnosis to the date of disease progression/relapse, the date of death, or the date of last contact. The log-rank test was used to compare the PFS distributions of ERBB2 groups.
Progression-Free Survival (PFS) Compared Between ERBB2 Assessment and Risk Group.
Time frame: 2 years after tumor cell analysis in 122 participants
122 participants with a diagnosis of medulloblastoma were grouped by ERBB2 positive/negative assessment and risk group into 4 groups. Progression-free survival was calculated from the date of diagnosis to the date of disease progression/relapse, the date of death, or the date of last contact. The log-rank test was used to compare the PFS distributions of ERBB2 groups.
Frequency of Mutations Associated With SHH and WNT Tumors
Time frame: within 3.5 years following completion of accrual
The frequency of mutations for the main genes associated with SHH and WNT tumors identified via targeted sequencing based on formalin fixed paraffin embedded material is provided.
8 secondary outcomes
Reading Decoding Composite Scores in the Intervention and Standard of Care Groups
Time frame: 5 years postdiagnosis
Number of Average Risk Patients Whose Treatment Failure Included the Posterior Fossa
Time frame: Annually for 6 years post irradiation
Associative Memory for Two Risk Group at Enrollment
Time frame: At enrollment
Associative Memory for Two Risk Group at 5 Years After Enrollment
Time frame: At 5 years after enrollment
Processing Speed for Two Risk Group at Enrollment
Time frame: At enrollment
Processing Speed for Two Risk Group at 5 Years After Enrollment
Time frame: At 5 years after enrollment
Perceptual Speed for Two Risk Group at Enrollment
Time frame: At enrollment
Perceptual Speed for Two Risk Group at 5 Years After Enrollment
Time frame: At 5 years after enrollment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34714708Acharya S, Guo Y, Patni T, Li Y, Wang C, Gargone M, Ashford JM, Wilson L, Faught A, Reddick WE, Patay Z, Gajjar A, Conklin HM, Merchant TE. Association Between Brain Substructure Dose and Cognitive Outcomes in Children With Medulloblastoma Treated on SJMB03: A Step Toward Substructure-Informed Planning. J Clin Oncol. 2022 Jan 1;40(1):83-95. doi: 10.1200/JCO.21.01480. Epub 2021 Oct 29.
- Derived from this study: PubMed 33743477Partanen M, Anghelescu DL, Hall L, Schreiber JE, Rossi M, Gajjar A, Jacola LM. Longitudinal associations between exposure to anesthesia and neurocognitive functioning in pediatric medulloblastoma. Eur J Cancer. 2021 May;148:103-111. doi: 10.1016/j.ejca.2021.02.010. Epub 2021 Mar 17.
- Derived from this study: PubMed 33502920Kumar 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.
- Derived from this study: PubMed 33405951Gajjar A, Robinson GW, Smith KS, Lin T, Merchant TE, Chintagumpala M, Mahajan A, Su J, Bouffet E, Bartels U, Schechter T, Hassall T, Robertson T, Nicholls W, Gururangan S, Schroeder K, Sullivan M, Wheeler G, Hansford JR, Kellie SJ, McCowage G, Cohn R, Fisher MJ, Krasin MJ, Stewart CF, Broniscer A, Buchhalter I, Tatevossian RG, Orr BA, Neale G, Klimo P Jr, Boop F, Srinivasan A, Pfister SM, Gilbertson RJ, Onar-Thomas A, Ellison DW, Northcott PA. Outcomes by Clinical and Molecular Features in Children With Medulloblastoma Treated With Risk-Adapted Therapy: Results of an International Phase III Trial (SJMB03). J Clin Oncol. 2021 Mar 1;39(7):822-835. doi: 10.1200/JCO.20.01372. Epub 2021 Jan 6.
- Derived from this study: PubMed 25665007Xu H, Robinson GW, Huang J, Lim JY, Zhang H, Bass JK, Broniscer A, Chintagumpala M, Bartels U, Gururangan S, Hassall T, Fisher M, Cohn R, Yamashita T, Teitz T, Zuo J, Onar-Thomas A, Gajjar A, Stewart CF, Yang JJ. Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss. Nat Genet. 2015 Mar;47(3):263-6. doi: 10.1038/ng.3217. Epub 2015 Feb 9.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amar Gajjar, MD principal investigator
St. Jude Children's Research Hospital
9 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing filgrastim, cisplatin and cyclophosphamide in people with Brain and Central Nervous System Tumors, run by St. Jude Children's Research Hospital at 9 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) in ERBB2-Negative Tumors Compared to ERBB2-Positive Tumors (time frame: 2 years after tumor cell analysis in 122 participants). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00085202, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2024.