Trial record 1 of 1 for:    ACNS0331
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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: May 18, 2016
Last verified: May 2016

June 14, 2004
May 18, 2016
April 2004
March 2016   (final data collection date for primary outcome measure)
Time to 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, assessed up to 3 years ] [ Designated as safety issue: No ]
Time-to-event for radiation therapy question will be based on logrank test. Interim monitoring for each study question will be based on the Lan-Demets criterion, with spending function αt. The time point for 100% information is defined as two years after the last patient has enrolled. Information expended will be computed based on the current available follow-up, using the parametric cure model for A9961.
Not Provided
Complete list of historical versions of study NCT00085735 on ClinicalTrials.gov Archive Site
  • Incidence of grade 3 and grade 4 toxicities in any body system as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events v 4.0 [ Time Frame: Through study completion, an average of 2 years ] [ Designated as safety issue: Yes ]
  • Local posterior fossa (LPF) failure [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    LPF failure is defined as tumor recurrence or progression within the tumor bed; i.e., within clinical target volume (CTV)boost 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.
  • Non-local posterior fossa (NLPF) failure [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    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
  • Non-posterior fossa (NPF) failure [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    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.
  • Post-treatment endocrine function (e.g., growth, sexual maturation, and need for hormone replacement) by laboratory assessment, clinical history, and exam [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    The analysis of toxicity and morbidity will compare the rates of adverse consequences of radiation therapy between treatment groups. The power of these comparisons can be demonstrated by reference to a two-sample test of means of normal random variables.
  • Post-treatment hearing loss as measure by audiogram or brainstem auditory evoked response (BAER) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    The analysis of toxicity and morbidity will compare the rates of adverse consequences of radiation therapy between treatment groups. The power of these comparisons can be demonstrated by reference to a two-sample test of means of normal random variables.
  • Post-treatment neurocognitive function as measured by neuropsychometric battery [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    The analysis of toxicity and morbidity will compare the rates of adverse consequences of radiation therapy between treatment groups. The power of these comparisons can be demonstrated by reference to a two-sample test of means of normal random variables.
  • Time to death from any cause [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Used to compute survival (S) percent.
  • Time to recurrence, progression, or death due to cancer [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Used to compute progression-free survival (PFS) percent. Death from causes that are clearly not associated with tumor recurrence or progression will be censored in this analysis.
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Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma
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
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.

PRIMARY OBJECTIVES:

I. Compare event-free and overall survival 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) and posterior fossa boost vs tumor bed boost radiotherapy (PFRT vs. IFRT) in combination with chemotherapy comprising vincristine, cisplatin, lomustine, and cyclophosphamide.

II. Compare event-free and overall survival of these patients (8 to 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 patterns of failure in patients treated with PFRT vs. IFRT. II. Compare the cognitive, auditory, and endocrinologic effects of these regimens in patients treated with SDCSI vs. LDCSI.

III. Compare the audiologic and endocrinologic toxicity from these regimens in patients treated with PFRT vs. IFRT.

IV. Develop an optimal gene expression medulloblastoma outcome predictor. V. Assess quality of life and functional status in patients treated with these regimens.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Untreated Childhood Medulloblastoma
  • 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
  • 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 I (3-7 years of age, LDCSI, IFRT)
    See Detailed Description (Arm I)
    Interventions:
    • Drug: Cisplatin
    • Radiation: Craniospinal Irradiation
    • Drug: Cyclophosphamide
    • Radiation: Involved-Field Radiation Therapy
    • Other: Laboratory Biomarker Analysis
    • Drug: Lomustine
    • Other: Quality-of-Life Assessment
    • Drug: Vincristine Sulfate
  • Experimental: Arm II (3-7 years of age, LDCSI, PFRT)
    See Detailed Description (Arm II)
    Interventions:
    • Drug: Cisplatin
    • Radiation: Craniospinal Irradiation
    • Drug: Cyclophosphamide
    • Other: Laboratory Biomarker Analysis
    • Drug: Lomustine
    • Other: Quality-of-Life Assessment
    • Radiation: Radiation Therapy
    • Drug: Vincristine Sulfate
  • Experimental: Arm III (3-7 years of age, SDCSI, IFRT)
    See Detailed Description (Arm III)
    Interventions:
    • Drug: Cisplatin
    • Radiation: Craniospinal Irradiation
    • Drug: Cyclophosphamide
    • Radiation: Involved-Field Radiation Therapy
    • Other: Laboratory Biomarker Analysis
    • Drug: Lomustine
    • Other: Quality-of-Life Assessment
    • Drug: Vincristine Sulfate
  • Active Comparator: Arm IV (3-7 years of age, SDCSI, PFRT)
    See Detailed Description (Arm IV)
    Interventions:
    • Radiation: Craniospinal Irradiation
    • Drug: Cyclophosphamide
    • Other: Laboratory Biomarker Analysis
    • Drug: Lomustine
    • Other: Quality-of-Life Assessment
    • Radiation: Radiation Therapy
    • Drug: Vincristine Sulfate
  • Experimental: Arm V (8-21 years of age, SDCSI, IFRT)
    See Detailed Description (Arm V)
    Interventions:
    • Drug: Cisplatin
    • Radiation: Craniospinal Irradiation
    • Drug: Cyclophosphamide
    • Radiation: Involved-Field Radiation Therapy
    • Other: Laboratory Biomarker Analysis
    • Drug: Lomustine
    • Other: Quality-of-Life Assessment
    • Drug: Vincristine Sulfate
  • Active Comparator: Arm VI (8-21 years of age, SDCSI, PFRT)
    See Detailed Description (Arm VI)
    Interventions:
    • Drug: Cisplatin
    • Radiation: Craniospinal Irradiation
    • Drug: Cyclophosphamide
    • Other: Laboratory Biomarker Analysis
    • Drug: Lomustine
    • Other: Quality-of-Life Assessment
    • Radiation: Radiation Therapy
    • Drug: Vincristine Sulfate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
528
Not Provided
March 2016   (final data collection date for primary outcome measure)

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
Both
3 Years to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   Netherlands,   New Zealand,   Switzerland
Puerto Rico
 
NCT00085735
ACNS0331, NCI-2009-00335, COG-ACNS0331, ACNS0331, CDR0000365506, ACNS0331, ACNS0331, U10CA098543
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Not Provided
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Jeff Michalski Children's Oncology Group
Children's Oncology Group
May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP