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Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00085735
First received: June 14, 2004
Last updated: February 9, 2017
Last verified: February 2017
  Purpose
This randomized phase III trial is studying how well standard-dose radiation therapy works compared to reduced-dose radiation therapy in children 3-7 years of age AND how well standard volume boost radiation therapy works compared to smaller volume boost radiation therapy when given together with chemotherapy in treating young patients who have undergone surgery for newly diagnosed standard-risk medulloblastoma. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as vincristine, cisplatin, lomustine, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy with chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether standard-dose radiation therapy is more effective than reduced-dose radiation therapy when given together with chemotherapy after surgery in treating young patients with medulloblastoma.

Condition Intervention Phase
Untreated Childhood Medulloblastoma
Drug: Cisplatin
Radiation: Craniospinal Irradiation
Drug: Cyclophosphamide
Radiation: Involved-Field Radiation Therapy
Other: Laboratory Biomarker Analysis
Drug: Lomustine
Other: Quality-of-Life Assessment
Radiation: Radiation Therapy
Drug: Vincristine Sulfate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Study Evaluating Limited Target Volume Boost Irradiation and Reduced Dose Craniospinal Radiotherapy (18.00 Gy) and Chemotherapy in Children With Newly Diagnosed Standard Risk Medulloblastoma: A Phase III Double Randomized Trial

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event-free survival (EFS) [ Time Frame: Time from study entry to disease progression, disease recurrence, death from any cause, or occurrence of a second malignant neoplasm, or to the date of last follow-up for patients without events Timeframe: Assessed at 3 years ]
    The primary statistical analysis for each of the two radiation therapy questions (IFRT vs. PFRT and LDCSI vs. SDCSI) will be based on a one-sided 1-beta confidence interval for the hazard ratio of the treatments. The analysis of CSI dose will be stratified on the PF volume, and the analysis of PF volume will be stratified by age group and CSI group. Intent to treat analysis will be used to evaluate the primary endpoints. All randomized eligible and evaluable patients (patients without disease dissemination or excess residual disease by central review and patients without anaplastic histology) will be included in these two comparisons.


Secondary Outcome Measures:
  • Time to death from any cause / overall survival (OS) [ Time Frame: Time from study entry to death from any cause or to the date of last follow-up for surviving patients Timeframe: Assessed at 3 years ]
    Used to compute overall survival (OS). Three-year OS rates will be reported. Comparisons of OS for each of the two radiation therapy questions (IFRT vs. PFRT and LDCSI vs. SDCSI) will be based on one-sided log rank tests. The analysis of CSI dose will be stratified on the PF volume and the analysis of PF volume will be stratified by age group (3-7 years vs. 8-21 years) and CSI group. Intent to treat analysis will be used. All randomized eligible and evaluable patients (patients without disease dissemination or excess residual disease by central review and patients without anaplastic histology) will be included in the two survival comparisons.

  • Local posterior fossa (LPF) failure rate [ Time Frame: Up to 3 years ]
    LPF failure is defined as tumor recurrence or progression within the tumor bed; i.e., within clinical target volume CTVboost for patients randomized to tumor-bed-only (involved field) boost (or within a theoretical CTVboost for patients randomized to standard PF radiation therapy). Recurrent tumors that straddle the boundary of CTVboost will be classified as LPF if more than 50% of the tumor volume is within CTVboost All randomized eligible and evaluable patients (patients without disease dissemination or excess residual disease by central review and patients without anaplastic histology) will be included. Three-year LPF failure rates will be reported separately for IFRT vs. PFRT patients.

  • Non-local posterior fossa (NLPF) failure rate [ Time Frame: Up to 3 years ]

    NLPF failure is defined as tumor outside CTVboost, but within CTVPF. Recurrent tumors that straddle the boundary of CTVboost will be classified as non-local posterior fossa (NLPF) if more than 50% of the tumor volume is outside of CTVboost. Recurrent tumors that straddle the boundary of CTVPF will be classified as LPF if more than 50% of the tumor volume is within CTVPF.

    All randomized eligible and evaluable patients (patients without disease dissemination or excess residual disease by central review and patients without anaplastic histology) will be included. Three-year NLPF failure rates will be reported separately for IFRT vs. PFRT patients.


  • Non-posterior fossa (NPF) failure rate [ Time Frame: Up to 3 years ]

    NPF is defined as tumor recurrence within the neuroaxis but outside of CTVPF. Recurrent tumors that straddle the boundary of CTVPF will be classified as NPF if more than 50% of the tumor volume is outside of CTVPF.

    All randomized eligible and evaluable patients (patients without disease dissemination or excess residual disease by central review and patients without anaplastic histology) will be included. Three-year NPF failure rates will be reported separately for IFRT vs. PFRT patients.


  • Post-treatment endocrine function (growth hormone (GH) and thyroid stimulating hormone (TSH)) as measured by laboratory assessment) . [ Time Frame: Up to 3 years ]
    Growth hormone stimulation tests were performed and noted as normal or abnormal at baseline and after completion of therapy/follow-up. Proportions of patients with abnormal results after completion of therapy will be calculated and reported separately for LDCSI vs. SDCSI patients. Mean post-treatment TSH levels will be reported by CSI group. Eligible and evaluable patients 3-7 years of age will be used.

  • Post-treatment grade 3+ hearing loss as measured by CTCAE v4 [ Time Frame: Up to 1 year after the end of treatment ]
    Proportions of patients with grade 3+ hearing loss after the completion of therapy will be calculated and reported separately for LDCSI vs. SDCSI patients. Eligible and evaluable patients 3-7 years of age will be used.

  • Post-treatment neurocognitive function as measured by the estimated full-scale IQ (FSIQ) and also the metacognition index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) [ Time Frame: Up to 6 years post-diagnosis ]
    Average scores for FSIQ and MI will be reported at each of the 3 neurocognitive assessment time points by LDCSI vs. SDCSI groups. All eligible and evaluable patients 3-7 years of age will be used.

  • Incidence of grade 3+ hearing loss at 1-year post treatment as assessed by CTCAE Version 4 [ Time Frame: 1 year after end of treatment ]
    Incidence rates will be reported separately for eligible and evaluable IFRT and PFRT patients.

  • Incidence of endocrine dysfunction as measured by growth hormone stimulation test at the completion of therapy. [ Time Frame: After completion of therapy, an average of 2 years ]
    Incidence rates of abnormal growth hormone stimulation tests at the after completion of therapy assessment will be reported separately for eligible and evaluable IFRT and PFRT patients.

  • Time to death from any cause / overall survival (OS) by molecular subgroup based on methylation arrays [ Time Frame: Assessed at 3 years ]
    Three-year survival rates will be reported by methylation subgroup. Randomized eligible and evaluable patients (patients without disease dissemination or excess residual disease by central review and patients without anaplastic histology) will be included.

  • Time to recurrence, progression or death due to cancer / progression-free survival (PFS) by molecular subgroup based on methylation arrays [ Time Frame: Assessed at 3 years ]

    Time from study entry to disease progression, relapse or death due to cancer or to last follow-up. Deaths from causes that are clearly not associated with tumor recurrence or progression and second malignancies will be censored.

    Three-year PFS rates will be reported by methylation subgroup. Randomized eligible and evaluable patients (patients without disease dissemination or excess residual disease by central review and patients without anaplastic histology) will be included.


  • Compliance rates for all eligible and evaluable patients enrolled [ Time Frame: Up to 6 years post-diagnosis ]

    A patient will be considered to be compliant if the patient/parent participated in the PedsQLTM v4 and the ABAS assessment. The patient should have a PedsQL total score which measures quality of life and a general adaptive composite (GAC) score which measures adaptive functioning. Compliance rates will be assessed at each of the 3 neurocognitive/quality of life assessment time points.

    All eligible and evaluable patients enrolled on ACNS0331 will be used. Patients removed from treatment prior to the time of neuropsychological assessment (for reasons such as disease progression, death, withdrawal of consent, etc.) will not be included in the denominator to assess the compliance rate.



Enrollment: 549
Study Start Date: April 2004
Study Completion Date: March 2016
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (3-7 years of age, LDCSI, IFRT)
See Detailed Description (Arm I)
Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Radiation: Craniospinal Irradiation
Undergo craniospinal Irradiation
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Radiation: Involved-Field Radiation Therapy
Undergo smaller volume boost (involved-field radiation therapy)
Other Names:
  • IFRT
  • Involved field radiotherapy
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Lomustine
Given orally
Other Names:
  • 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea
  • 1-Nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-
  • Belustin
  • Belustine
  • CCNU
  • Cecenu
  • CeeNU
  • Chloroethylcyclohexylnitrosourea
  • Citostal
  • Lomeblastin
  • Lomustinum
  • Lucostin
  • Lucostine
  • N-(2-Chloroethyl)-N'-cyclohexyl-N-nitrosourea
  • Prava
  • RB-1509
  • WR-139017
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
Experimental: Arm II (3-7 years of age, LDCSI, PFRT)
See Detailed Description (Arm II)
Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Radiation: Craniospinal Irradiation
Undergo craniospinal Irradiation
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Lomustine
Given orally
Other Names:
  • 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea
  • 1-Nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-
  • Belustin
  • Belustine
  • CCNU
  • Cecenu
  • CeeNU
  • Chloroethylcyclohexylnitrosourea
  • Citostal
  • Lomeblastin
  • Lomustinum
  • Lucostin
  • Lucostine
  • N-(2-Chloroethyl)-N'-cyclohexyl-N-nitrosourea
  • Prava
  • RB-1509
  • WR-139017
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Radiation: Radiation Therapy
Undergo standard volume boost (whole posterior fossa radiation therapy)
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RADIATION
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
Experimental: Arm III (3-7 years of age, SDCSI, IFRT)
See Detailed Description (Arm III)
Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Radiation: Craniospinal Irradiation
Undergo craniospinal Irradiation
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Radiation: Involved-Field Radiation Therapy
Undergo smaller volume boost (involved-field radiation therapy)
Other Names:
  • IFRT
  • Involved field radiotherapy
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Lomustine
Given orally
Other Names:
  • 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea
  • 1-Nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-
  • Belustin
  • Belustine
  • CCNU
  • Cecenu
  • CeeNU
  • Chloroethylcyclohexylnitrosourea
  • Citostal
  • Lomeblastin
  • Lomustinum
  • Lucostin
  • Lucostine
  • N-(2-Chloroethyl)-N'-cyclohexyl-N-nitrosourea
  • Prava
  • RB-1509
  • WR-139017
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
Active Comparator: Arm IV (3-7 years of age, SDCSI, PFRT)
See Detailed Description (Arm IV)
Radiation: Craniospinal Irradiation
Undergo craniospinal Irradiation
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Lomustine
Given orally
Other Names:
  • 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea
  • 1-Nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-
  • Belustin
  • Belustine
  • CCNU
  • Cecenu
  • CeeNU
  • Chloroethylcyclohexylnitrosourea
  • Citostal
  • Lomeblastin
  • Lomustinum
  • Lucostin
  • Lucostine
  • N-(2-Chloroethyl)-N'-cyclohexyl-N-nitrosourea
  • Prava
  • RB-1509
  • WR-139017
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Radiation: Radiation Therapy
Undergo standard volume boost (whole posterior fossa radiation therapy)
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RADIATION
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
Experimental: Arm V (8-21 years of age, SDCSI, IFRT)
See Detailed Description (Arm V)
Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Radiation: Craniospinal Irradiation
Undergo craniospinal Irradiation
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Radiation: Involved-Field Radiation Therapy
Undergo smaller volume boost (involved-field radiation therapy)
Other Names:
  • IFRT
  • Involved field radiotherapy
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Lomustine
Given orally
Other Names:
  • 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea
  • 1-Nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-
  • Belustin
  • Belustine
  • CCNU
  • Cecenu
  • CeeNU
  • Chloroethylcyclohexylnitrosourea
  • Citostal
  • Lomeblastin
  • Lomustinum
  • Lucostin
  • Lucostine
  • N-(2-Chloroethyl)-N'-cyclohexyl-N-nitrosourea
  • Prava
  • RB-1509
  • WR-139017
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
Active Comparator: Arm VI (8-21 years of age, SDCSI, PFRT)
See Detailed Description (Arm VI)
Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Radiation: Craniospinal Irradiation
Undergo craniospinal Irradiation
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Lomustine
Given orally
Other Names:
  • 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea
  • 1-Nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-
  • Belustin
  • Belustine
  • CCNU
  • Cecenu
  • CeeNU
  • Chloroethylcyclohexylnitrosourea
  • Citostal
  • Lomeblastin
  • Lomustinum
  • Lucostin
  • Lucostine
  • N-(2-Chloroethyl)-N'-cyclohexyl-N-nitrosourea
  • Prava
  • RB-1509
  • WR-139017
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Radiation: Radiation Therapy
Undergo standard volume boost (whole posterior fossa radiation therapy)
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RADIATION
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate

  Hide Detailed Description

Detailed Description:

PRIMARY OBJECTIVES:

I. Compare event-free survival (EFS) of pediatric patients (3 to 7 years of age) with newly diagnosed standard-risk medulloblastoma treated with standard-dose versus (vs.) reduced-dose craniospinal radiotherapy (SDCSI vs. LDCSI).

II. Compare EFS of patients (3-21 years of age) treated with standard-dose craniospinal radiotherapy and posterior fossa boost vs tumor bed boost radiotherapy in combination with this chemotherapy regimen.

SECONDARY OBJECTIVES:

I. Compare overall survival (OS) of pediatric patients (3-7 years of age) with newly diagnosed standard-risk medulloblastoma treated with SDCSI vs. LDCSI.

II. Compare OS of patients (3-21 years of age) with newly diagnosed standard-risk medulloblastoma treated with PFRT vs. IFRT.

III. To evaluate patterns of failure in patients treated with an irradiation boost volume smaller than conventional posterior fossa volumes.

IV. To reduce the cognitive, auditory, and endocrinologic effects of treatment of average-risk medulloblastoma by reducing the dose of craniospinal irradiation therapy.

V. To determine if the audiologic and endocrinologic toxicity will be reduced with the use of limited tumor boost volume irradiation compared to patients treated with conventional target volumes of radiation.

VI. Develop an optimal gene expression medulloblastoma outcome predictor, validated prospectively in a multi-institution randomized clinical trial.

VII. To improve compliance with long-term quality of life (QoL) and functional status data submission by educating institutional nurses to administer and submit for analysis a battery of four instruments (Behavior Assessment System for Children- 2nd Edition (BASC-2), Adaptive Behavior Assessment System - 2nd Edition (ABAS-II), Behavior Rating Inventory of Executive Function (BRIEF) and PedsQLTM 4.0).

OUTLINE: Patients 3-7 years of age are randomized to 1 of 4 arms (Arm I-IV). Patients 8-21 years of age are randomized to 1 of 2 arms (Arm V or VI).

Within 31 days after definitive surgery, all patients begin therapy. Patients undergo radiation therapy with doses according to their Arm randomization on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). All patients receive vincristine intravenously (IV) over 1 minute (or infusion via minibag as per institutional policy) on days 8, 15, 22, 29, 36, and 43 (weeks 1-6).

ARM I: Patients 3-7 years of age undergo lowered dose craniospinal irradiation (LDCSI) with involved-field radiation therapy (IFRT) boost.

ARM II: Patients 3-7 years of age undergo LDCSI with whole posterior fossa radiation therapy (PFRT) boost.

ARM III: Patients 3-7 years of age undergo standard dose craniospinal irradiation (SDCSI) with IFRT boost.

ARM IV: Patients 3-7 years of age undergo SDCSI with PFRT boost.

ARM V: Patients 8-21 years of age undergo SDCSI with IFRT boost.

ARM VI: Patients 8-21 years of age undergo SDCSI with PFRT boost.

MAINTENANCE CHEMOTHERAPY: Beginning 4 weeks after completion of chemoradiotherapy, patients receive 2 different regimens of maintenance chemotherapy for a total of 9 courses. Each course in regimen A is 6 weeks (42 days) in duration. Each course in regimen B is 4 weeks (28 days) in duration.

REGIMEN A (courses 1, 2, 4, 5, 7, and 8): Patients receive lomustine orally and cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49.

REGIMEN B (courses 3, 6, and 9): Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine IV on days 1 and 8 of weeks 23, 39, and 55.

Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at 3-6 months after completion of radiotherapy and at 3-4 years after study entry. Neurocognitive function may also be assessed.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed medulloblastoma located in the posterior fossa

    • Standard-risk disease
  • Minimal volume, non-disseminated disease, defined by the following:

    • Residual tumor ≤ 1.5 cm^2 confirmed by MRI with contrast imaging within 21 days after surgery
    • No metastatic disease in the head, spine, or cerebrospinal fluid (CSF) confirmed by both of the following:

      • Enhanced MRI of the spine within 5 days before surgery OR within 28 days after surgery
      • Negative cytological examination of CSF after surgery, but before study enrollment
  • Brain stem involvement allowed
  • Performance status - Karnofsky 50-100% (> 16 years of age)
  • Performance status - Lansky 30-100% (≤ 16 years of age)
  • Absolute neutrophil count > 1,500/uL
  • Platelet count > 100,000/uL (transfusion independent)
  • Hemoglobin > 10 g/dL (transfusions allowed)
  • Bilirubin < 1.5 times upper limit of normal (ULN) for age
  • AST or ALT < 1.5 times ULN for age
  • Creatinine clearance OR radioisotope glomerular filtration rate >= 70 mL/min/1.73m^2 or a serum creatinine based on age/gender as follows:

Age Maximum Serum Creatine (mg/dL)

  • 1month to < 6 months male: 0.4 female: 0.4
  • 6 months to <1 year male: 0.5 female: 0.5
  • 1 year to < 2 years male: 0.6 female: 0.6
  • 2 to < 6 years male: 0.8 female: 0.8
  • 6 to < 10 years male: 1 female: 1
  • 10 to < 13 years male: 1.2 female: 1.2
  • 13 to < 16 years male: 1.5 female: 1.4
  • >= 16 years male: 1.7 female: 1.4

    • Not pregnant or nursing
    • Negative pregnancy test
    • Fertile patients must use effective contraception
    • No prior chemotherapy
    • Prior corticosteroids allowed
    • No prior radiotherapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00085735

  Show 178 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Jeff Michalski Children's Oncology Group
  More Information

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00085735     History of Changes
Other Study ID Numbers: ACNS0331  NCI-2009-00335  COG-ACNS0331  CDR0000365506  ACNS0331  ACNS0331  U10CA098543 
Study First Received: June 14, 2004
Last Updated: February 9, 2017

Additional relevant MeSH terms:
Medulloblastoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neuroectodermal Tumors, Primitive
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cyclophosphamide
Lomustine
Vincristine
Cisplatin
Succinylcholine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Neuromuscular Depolarizing Agents
Neuromuscular Blocking Agents

ClinicalTrials.gov processed this record on February 28, 2017