Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor
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 |
---|---|---|
|
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
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:
Drug: cisplatin
Given IV
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: vincristine
Given IV
Other Names:
Procedure: autologous hematopoietic stem cell transplantation
Patients undergo autologous stem cell transplantation
Other Names:
Radiation: radiation therapy
Patients undergo craniospinal radiotherapy once daily 5 days a week for 6 weeks.
Other Names:
|
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:
Drug: cisplatin
Given IV
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: vincristine
Given IV
Other Names:
Procedure: autologous hematopoietic stem cell transplantation
Patients undergo autologous stem cell transplantation
Other Names:
Radiation: radiation therapy
Patients undergo craniospinal radiotherapy once daily 5 days a week for 6 weeks.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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.
- 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
- 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.
- 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.
- 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
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:
Publications
None provided.- SJMB03
- NCI-2011-01185
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
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 |
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 |
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
|
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 |
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 |
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
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.
Results Point of Contact
Name/Title | Amar Gajjar, MD |
---|---|
Organization | St. Jude Children's Research Hospital |
Phone | 866-278-5833 |
info@stjude.org |
- SJMB03
- NCI-2011-01185