Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor

• Sponsor: St. Jude Children's Research Hospital (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00085202
• Collaborator: (none)
• Enrollment: 416
• Locations: 9
• Arms: 2
• Duration (Months): 233
• Patients Per Site: 46.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief 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. 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).

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Biological: filgrastim; Drug: cisplatin; Drug: cyclophosphamide; Drug: vincristine; Procedure: autologous hematopoietic stem cell transplantation; Radiation: radiation therapy	Phase 3

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

• Study Type: Interventional
• Actual Enrollment: 416 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor
• Study Start Date: Aug 1, 2003
• Actual Primary Completion Date: Dec 1, 2016
• Anticipated Study Completion Date: Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stratum 1 (high-risk group) 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	Biological: filgrastim; Given subcutaneously; Other Names: Neupogen(R) G-CSF ; Drug: cisplatin; Given IV; Other Names: Platinol-AQ(R) ; Drug: cyclophosphamide; Given IV; Other Names: Cytoxan(R) ; Drug: vincristine; Given IV; Other Names: Oncovin(R) ; Procedure: autologous hematopoietic stem cell transplantation; Patients undergo autologous stem cell transplantation; Other Names: autologous HSCT ; Radiation: radiation therapy; Patients undergo craniospinal radiotherapy once daily 5 days a week for 6 weeks.; Other Names: RT Craniospinal radiotherapy
Experimental: Stratum 2 (average-risk group) 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	Biological: filgrastim; Given subcutaneously; Other Names: Neupogen(R) G-CSF ; Drug: cisplatin; Given IV; Other Names: Platinol-AQ(R) ; Drug: cyclophosphamide; Given IV; Other Names: Cytoxan(R) ; Drug: vincristine; Given IV; Other Names: Oncovin(R) ; Procedure: autologous hematopoietic stem cell transplantation; Patients undergo autologous stem cell transplantation; Other Names: autologous HSCT ; Radiation: radiation therapy; Patients undergo craniospinal radiotherapy once daily 5 days a week for 6 weeks.; Other Names: RT Craniospinal radiotherapy

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) in ERBB2-Negative Tumors Compared to ERBB2-Positive Tumors [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.

2. Progression-Free Survival (PFS) Compared Between ERBB2 Assessment and Risk Group. [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.

3. Frequency of Mutations Associated With SHH and WNT Tumors [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.

Secondary Outcome Measures

1. Reading Decoding Composite Scores in the Intervention and Standard of Care Groups [Measurements will be made at time of randomization, at 3 months from initiation of treatment, and yearly thereafter for up to 10 years]

   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.

2. Number of Average Risk Patients Whose Treatment Failure Included the Posterior Fossa [Annually for 6 years post irradiation]

   To monitor for treatment failure in the posterior fossa of patients whose tumor bed receives a reduced volume of radiation.

3. Longitudinal Change in Functional Outcomes by Mean RT Dose to Specified Target Tissues [Once all patients have been followed for 2 years]

   To correlate radiation dosimetry of target and normal tissues with rate and patterns of failure and longitudinal measures of audiometric, endocrine and cognitive effects.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
2	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
3	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
4	Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital	Houston	Texas	United States	77030-2399
5	Sydney Children's Hospital	Randwick	New South Wales	Australia	2031
6	Children's Hospital at Westmead	Westmead	New South Wales	Australia	2145
7	Lady Cilento Children's Hospital, Brisbane	Brisbane	Queensland	Australia	4029
8	Royal Children's Hospital	Parkville	Victoria	Australia	3052
9	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8

Sponsors and Collaborators

• St. Jude Children's Research Hospital

Investigators

• Principal Investigator: Amar Gajjar, MD, St. Jude Children's Research Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT00085202
• Other Study ID Numbers: SJMB03; NCI-2011-01185
• First Posted: Jun 11, 2004
• Last Update Posted: Jan 6, 2022
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by St. Jude Children's Research Hospital: untreated childhood medulloblastoma; untreated childhood supratentorial primitive neuroectodermal tumor; childhood atypical teratoid/rhabdoid tumor; untreated childhood pineoblastoma
• Additional relevant MeSH terms: Nervous System Neoplasms; Central Nervous System Neoplasms; Medulloblastoma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Rhabdoid Tumor; Cyclophosphamide; Vincristine

Study Results

Participant Flow

Recruitment Details	416 participants were enrolled between 9/9/2003 and 3/7/2013.
Pre-assignment Detail	Of the 416 participants enrolled, three were ineligible and taken off study.

Arm/Group Title	Average-Risk Group	High-Risk Group
Arm/Group Description	Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa (or supratentorial compartment for PNET's/ATRT). Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was <1.5 cm^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size <1.5 cm^2).	Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm^2) at the primary site after surgery.
Period Title: Overall Study
STARTED	269	144
COMPLETED	251	120
NOT COMPLETED	18	24

Baseline Characteristics

Arm/Group Title	Average-Risk Group	High-Risk Group	Total
Arm/Group Description	Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa (or supratentorial compartment for PNET's/ATRT). Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was <1.5 cm^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size <1.5 cm^2).	Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm^2) at the primary site after surgery.	Total of all reporting groups
Overall Participants	269	144	413
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	9.15 (4.08)	8.66 (3.93)	8.98 (4.03)
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	8.42	7.87	8.33
Sex: Female, Male (Count of Participants)
Female	105 39%	56 38.9%	161 39%
Male	164 61%	88 61.1%	252 61%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) in ERBB2-Negative Tumors Compared to ERBB2-Positive Tumors
Description	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.
Time Frame	2 years after tumor cell analysis in 122 participants

Outcome Measure Data

Analysis Population Description

Analysis included the first 122 participants with a diagnosis of medulloblastoma and with fresh tissue and ERBB2 protein assessments. Participants with a diagnosis of PNET, PNET variants, or ATRT were not included in this analysis.

Arm/Group Title	Overall Study	Average-Risk Group	High-Risk Group
Arm/Group Description	Analysis included the first 122 participants with a diagnosis of medulloblastoma and with fresh tissue and ERBB2 protein assessments. Participants with a diagnosis of supratentorial primitive neuroectodermal tumor (PNET), PNET variants (ependymoblastoma, pineoblastoma, CNS neuroblastoma), or atypical teratoid rhabdoid tumor (ATRT) were not included in the analysis of ERBB2 tumors.	Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was <1.5 cm^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size <1.5 cm^2).	Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm^2) at the primary site after surgery.
Measure Participants	122	85	37
Positive ERBB2 (77, 54, 23)	0.792 (0.045)	0.833 (0.050)	0.696 (0.096)
Negative ERBB2 (45, 31, 14)	0.867 (0.050)	0.935 (0.043)	0.714 (0.115)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Overall Study
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8001
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Average-Risk Group
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5195
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	High-Risk Group
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7696
	Comments
	Method	Log Rank
	Comments

2. Primary Outcome

Title	Progression-Free Survival (PFS) Compared Between ERBB2 Assessment and Risk Group.
Description	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.
Time Frame	2 years after tumor cell analysis in 122 participants

Outcome Measure Data

Analysis Population Description

Analysis was completed for the first 122 participants with a diagnosis of medulloblastoma and with fresh tissue and ERBB2 protein assessments. Participants with a diagnosis of PNET, PNET variants, or ATRT were not included in this analysis.

Arm/Group Title	ERBB2 Positive & Average Risk	ERBB2 Positive & High Risk	ERBB2 Negative & Average Risk	ERBB2 Negative & High Risk
Arm/Group Description	54 participants who were ERBB2 positive and in the average risk group.	23 participants who were ERBB2 positive and in the high risk group	31 participants who were ERBB2 negative and in the average risk group	14 participants who were ERBB2 negative and in the high risk group
Measure Participants	54	23	31	14
Mean (Standard Error) [percentage of participants]	0.833 (0.050) 0.3%	0.696 (0.096) 0.5%	0.935 (0.043) 0.2%	0.714 (0.115) NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Overall Study, Average-Risk Group, High-Risk Group, ERBB2 Negative & High Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0206
	Comments
	Method	Log Rank
	Comments

3. Primary Outcome

Title	Frequency of Mutations Associated With SHH and WNT Tumors
Description	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.
Time Frame	within 3.5 years following completion of accrual

Outcome Measure Data

Analysis Population Description

Only patients with WNT and SHH tumors with available tissue for targeted sequencing were analyzed for frequency of mutation. WNT and SHH subgroups were identified by methylation profiling.

Arm/Group Title	SHH Pathway - In/Del Somatic	WNT Pathway - In/Del Somatic	SHH Pathway - In/Del Germline	WNT Pathway - In/Del Germline	SHH Pathway - SNV Somatic	WNT Pathway - SNV Somatic	SHH Pathway - SNV Germline	WNT Pathway - SNV Germline
Arm/Group Description	Tissue from this subgroup of patients was analyzed for somatic insertion/deletion (In/Del).	Tissue from this subgroup of patients was analyzed for somatic insertion/deletion (In/Del).	Tissue from this subgroup of patients was analyzed for germline insertion/deletion (In/Del).	Tissue from this subgroup of patients was analyzed for germline insertion/deletion (In/Del).	Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).	Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).
Measure Participants	20	18	20	18	20	18	20	18
PTCH1	7 2.6%	0 0%	0 0%	0 NaN	4 NaN	0 NaN	0 NaN	0 NaN
DDX3X	0 0%	0 0%	0 0%	0 NaN	3 NaN	7 NaN	0 NaN	0 NaN
TP53	0 0%	0 0%	0 0%	0 NaN	5 NaN	3 NaN	0 NaN	0 NaN
KMT2D	2 0.7%	2 1.4%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
SUFU	2 0.7%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
CREBBP	1 0.4%	2 1.4%	0 0%	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN
GLI2	0 0%	0 0%	0 0%	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN
TCF4	0 0%	0 0%	0 0%	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN
PTEN	0 0%	0 0%	0 0%	0 NaN	3 NaN	0 NaN	0 NaN	0 NaN
KMT2C	0 0%	1 0.7%	0 0%	0 NaN	2 NaN	1 NaN	0 NaN	0 NaN
FBXW7	0 0%	0 0%	0 0%	0 NaN	1 NaN	4 NaN	0 NaN	0 NaN
GSE1	3 1.1%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
CTNNB1	0 0%	0 0%	0 0%	0 NaN	1 NaN	18 NaN	0 NaN	0 NaN
SMARCA4	0 0%	0 0%	0 0%	0 NaN	0 NaN	4 NaN	0 NaN	0 NaN
PIK3CA	0 0%	0 0%	0 0%	0 NaN	2 NaN	1 NaN	0 NaN	0 NaN
APC	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	1 NaN
EPHA7	0 0%	1 0.7%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
ARID1A	0 0%	1 0.7%	0 0%	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN
ARID2	0 0%	0 0%	0 0%	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN
ATM	0 0%	0 0%	0 0%	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN
BRCA2	0 0%	0 0%	1 0.2%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN

4. Secondary Outcome

Title	Reading Decoding Composite Scores in the Intervention and Standard of Care Groups
Description	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.
Time Frame	Measurements will be made at time of randomization, at 3 months from initiation of treatment, and yearly thereafter for up to 10 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Number of Average Risk Patients Whose Treatment Failure Included the Posterior Fossa
Description	To monitor for treatment failure in the posterior fossa of patients whose tumor bed receives a reduced volume of radiation.
Time Frame	Annually for 6 years post irradiation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Longitudinal Change in Functional Outcomes by Mean RT Dose to Specified Target Tissues
Description	To correlate radiation dosimetry of target and normal tissues with rate and patterns of failure and longitudinal measures of audiometric, endocrine and cognitive effects.
Time Frame	Once all patients have been followed for 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment.
Adverse Event Reporting Description	Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Arm/Group Title	Average-Risk Group		High-Risk Group
Arm/Group Description	Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa (or supratentorial compartment for PNET's/ATRT). Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was <1.5 cm^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size <1.5 cm^2).		Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm^2) at the primary site after surgery.
All Cause Mortality
	Average-Risk Group		High-Risk Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Average-Risk Group		High-Risk Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/269 (6.3%)		17/144 (11.8%)
Cardiac disorders
Supraventricular and nodal arrhythmia - sinus bradycardia	0/269 (0%)	0	1/144 (0.7%)	1
Cardiac general - other	0/269 (0%)	0	1/144 (0.7%)	1
Pericardial effusion (non-malignant)	1/269 (0.4%)	1	0/144 (0%)	0
General disorders
Death not associated with CTCAE term, death NOS	0/269 (0%)	0	1/144 (0.7%)	1
Syndromes - other	1/269 (0.4%)	1	1/144 (0.7%)	1
Pain - other	0/269 (0%)	0	1/144 (0.7%)	1
Hepatobiliary disorders
Cholecystitis	0/269 (0%)	0	1/144 (0.7%)	1
Pancreatitis	1/269 (0.4%)	1	0/144 (0%)	0
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	1/269 (0.4%)	1	0/144 (0%)	0
Infections and infestations
Febrile neutropenia	2/269 (0.7%)	2	0/144 (0%)	0
Infection, blood	1/269 (0.4%)	1	0/144 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils, blood	0/269 (0%)	0	2/144 (1.4%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils, lung (pneumonia)	1/269 (0.4%)	1	0/144 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils, meninges (meningitis)	0/269 (0%)	0	1/144 (0.7%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils, wound	0/269 (0%)	0	1/144 (0.7%)	1
Infection with unknown ANC, meninges (meningitis)	2/269 (0.7%)	2	0/144 (0%)	0
Infection with unknown ANC, wound	0/269 (0%)	0	1/144 (0.7%)	1
Metabolism and nutrition disorders
Acidosis (metabolic or respiratory)	1/269 (0.4%)	1	0/144 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal/soft tissue - other	1/269 (0.4%)	1	0/144 (0%)	0
Nervous system disorders
Apnea	0/269 (0%)	0	1/144 (0.7%)	1
CNS cerebrovascular ischemia	0/269 (0%)	0	1/144 (0.7%)	1
CNS necrosis/cystic progression	1/269 (0.4%)	1	3/144 (2.1%)	3
Cognitive disturbance	0/269 (0%)	0	1/144 (0.7%)	1
Confusion	0/269 (0%)	0	1/144 (0.7%)	1
Encephalopathy	0/269 (0%)	0	1/144 (0.7%)	1
Leak, cerebrospinal fluid (CSF)	0/269 (0%)	0	2/144 (1.4%)	2
Leukoencephalopathy (radiographic findings)	0/269 (0%)	0	1/144 (0.7%)	1
Neuropathy	0/269 (0%)	0	1/144 (0.7%)	1
Personality/behavioral	1/269 (0.4%)	1	0/144 (0%)	0
Seizure	3/269 (1.1%)	3	3/144 (2.1%)	3
Somnolence/depressed level of consciousness	0/269 (0%)	0	1/144 (0.7%)	1
Syncope (fainting)	1/269 (0.4%)	1	0/144 (0%)	0
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome (ARDS)	1/269 (0.4%)	1	0/144 (0%)	0
Hypoxia	1/269 (0.4%)	1	0/144 (0%)	0
Pleural effusion (non-malignant)	2/269 (0.7%)	2	0/144 (0%)	0
Pneumonitis/pulmonary infiltrates	1/269 (0.4%)	1	0/144 (0%)	0
Pneumothorax	1/269 (0.4%)	1	0/144 (0%)	0
Pulmonary fibrosis (radiographic changes)	1/269 (0.4%)	1	0/144 (0%)	0
Pulmonary/upper respiratory - other	1/269 (0.4%)	1	1/144 (0.7%)	1
Vascular disorders
Thrombotic microangiopathy	0/269 (0%)	0	1/144 (0.7%)	1
Hemorrhage/bleeding - other	0/269 (0%)	0	1/144 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Average-Risk Group		High-Risk Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	236/269 (87.7%)		118/144 (81.9%)
Cardiac disorders
Hypotension	16/269 (5.9%)	17	14/144 (9.7%)	19
Hypertension	15/269 (5.6%)	25	10/144 (6.9%)	12
Ear and labyrinth disorders
Hearing: patients with/without baseline audiogram and enrolled in a monitoring program	11/269 (4.1%)	12	9/144 (6.3%)	9
Gastrointestinal disorders
Vomiting	53/269 (19.7%)	63	21/144 (14.6%)	29
Nausea	27/269 (10%)	30	20/144 (13.9%)	23
Diarrhea	23/269 (8.6%)	36	14/144 (9.7%)	16
Anorexia	17/269 (6.3%)	17	12/144 (8.3%)	13
General disorders
Pain, abdomen NOS	33/269 (12.3%)	37	17/144 (11.8%)	30
Pain, head/headache	13/269 (4.8%)	13	10/144 (6.9%)	14
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	39/269 (14.5%)	54	23/144 (16%)	32
Infections and infestations
Febrile neutropenia	172/269 (63.9%)	383	77/144 (53.5%)	148
Infection, blood	55/269 (20.4%)	76	24/144 (16.7%)	28
Infection - other	25/269 (9.3%)	33	16/144 (11.1%)	19
Colitis, infectious (e.g., Clostridium difficile)	22/269 (8.2%)	28	7/144 (4.9%)	8
Infection with normal ANC or Grade 1 or 2 neutrophils, blood	21/269 (7.8%)	30	9/144 (6.3%)	11
Infection with unknown ANC, blood	17/269 (6.3%)	23	13/144 (9%)	19
Infection with normal ANC or Grade 1 or 2 neutrophils, catheter-related	16/269 (5.9%)	21	3/144 (2.1%)	3
Infection, catheter-related	14/269 (5.2%)	15	5/144 (3.5%)	7
Vascular disorders
Hemorrhage, pulmonary/upper respiratory, nose	14/269 (5.2%)	20	11/144 (7.6%)	16

Limitations/Caveats

The study is ongoing. Participant flow and adverse events will be updated as additional outcomes are reported.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.