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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00085735




Registration number
NCT00085735
Ethics application status
Date submitted
14/06/2004
Date registered
16/06/2004
Date last updated
5/11/2024

Titles & IDs
Public title
Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma
Scientific 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
Secondary ID [1] 0 0
NCI-2009-00335
Secondary ID [2] 0 0
ACNS0331
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Medulloblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Children's - Brain
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cisplatin
Treatment: Other - Craniospinal Irradiation
Treatment: Drugs - Cyclophosphamide
Treatment: Other - Involved-Field Radiation Therapy
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Lomustine
Other interventions - Quality-of-Life Assessment
Treatment: Other - Radiation Therapy
Treatment: Drugs - Vincristine Sulfate

Experimental: Arm I (3-7 years of age, LDCSI, IFRT) - See Detailed Description (Arm I)

Experimental: Arm II (3-7 years of age, LDCSI, PFRT) - See Detailed Description (Arm II)

Experimental: Arm III (3-7 years of age, SDCSI, IFRT) - See Detailed Description (Arm III)

Active comparator: Arm IV (3-7 years of age, SDCSI, PFRT) - See Detailed Description (Arm IV)

Experimental: Arm V (8-21 years of age, SDCSI, IFRT) - See Detailed Description (Arm V)

Active comparator: Arm VI (8-21 years of age, SDCSI, PFRT) - See Detailed Description (Arm VI)


Treatment: Drugs: Cisplatin
Given IV

Treatment: Other: Craniospinal Irradiation
Undergo craniospinal Irradiation

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Other: Involved-Field Radiation Therapy
Undergo smaller volume boost (involved-field radiation therapy)

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Lomustine
Given orally

Other interventions: Quality-of-Life Assessment
Ancillary studies

Treatment: Other: Radiation Therapy
Undergo standard volume boost (whole posterior fossa radiation therapy)

Treatment: Drugs: Vincristine Sulfate
Given IV
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Intervention code [3] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free Survival (EFS)
Timepoint [1] 0 0
Assessed at 3 years
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
3 years
Secondary outcome [1] 0 0
Local Posterior Fossa (LPF) Failure Rate
Timepoint [1] 0 0
3 years
Secondary outcome [2] 0 0
Non-local Posterior Fossa (NLPF) Failure Rate
Timepoint [2] 0 0
3 years
Secondary outcome [3] 0 0
Non-posterior Fossa (NPF) Failure Rate
Timepoint [3] 0 0
3 years
Secondary outcome [4] 0 0
Post-treatment Endocrine Function by CSI Group
Timepoint [4] 0 0
Up to 3 years
Secondary outcome [5] 0 0
Post-treatment Grade 3+ Hearing Loss as Measured by Common Terminology Criteria for Adverse Events (CTCAE) Version (v)4
Timepoint [5] 0 0
Up to 3 years
Secondary outcome [6] 0 0
Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 1 (4 - 15 Months Post Diagnosis).
Timepoint [6] 0 0
4 -15 months post diagnosis
Secondary outcome [7] 0 0
Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 2 (27 - 48 Months Post Diagnosis)
Timepoint [7] 0 0
27 - 48 months post diagnosis
Secondary outcome [8] 0 0
Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 3 (49 - 72 Months Post Diagnosis)
Timepoint [8] 0 0
49 - 72 months post diagnosis
Secondary outcome [9] 0 0
Incidence of Grade 3+ Hearing Loss at 1-year Post Treatment as Assessed by CTCAE v4
Timepoint [9] 0 0
Up to 3 years
Secondary outcome [10] 0 0
Incidence of Endocrine Dysfunction as Measured by Growth Hormone Stimulation Tests at the Time of Completion of Therapy by Radiotherapy (RT) Group
Timepoint [10] 0 0
Post-treatment up to 3 years
Secondary outcome [11] 0 0
Overall Survival (OS) by Molecular Subgroup Based on Methylation Arrays
Timepoint [11] 0 0
3 years
Secondary outcome [12] 0 0
Progression-free Survival (PFS) by Molecular Subgroup Based on Methylation Arrays
Timepoint [12] 0 0
3 years
Secondary outcome [13] 0 0
Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 1 (4-15 Months Post Diagnosis)
Timepoint [13] 0 0
4 - 15 months post diagnosis
Secondary outcome [14] 0 0
Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 2 (27-48 Months Post Diagnosis)
Timepoint [14] 0 0
27-48 months post diagnosis
Secondary outcome [15] 0 0
Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 3 (49 - 72 Months Post Diagnosis)
Timepoint [15] 0 0
49 - 72 months post diagnosis
Secondary outcome [16] 0 0
Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 1 (4-15 Months Post Diagnosis)
Timepoint [16] 0 0
4-15 months post diagnosis
Secondary outcome [17] 0 0
Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 2 (27-48 Months Post Diagnosis)
Timepoint [17] 0 0
27-48 months post diagnosis
Secondary outcome [18] 0 0
Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 3 (49 - 72 Months Post Diagnosis)
Timepoint [18] 0 0
49 - 72 months post diagnosis

Eligibility
Key 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
Minimum age
3 Years
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/04/2004
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
549
Recruitment in Australia
Recruitment state(s)
SA,WA
Recruitment hospital [1] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [2] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
5006 - North Adelaide
Recruitment postcode(s) [2] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Delaware
Country [7] 0 0
United States of America
State/province [7] 0 0
District of Columbia
Country [8] 0 0
United States of America
State/province [8] 0 0
Florida
Country [9] 0 0
United States of America
State/province [9] 0 0
Georgia
Country [10] 0 0
United States of America
State/province [10] 0 0
Hawaii
Country [11] 0 0
United States of America
State/province [11] 0 0
Idaho
Country [12] 0 0
United States of America
State/province [12] 0 0
Illinois
Country [13] 0 0
United States of America
State/province [13] 0 0
Indiana
Country [14] 0 0
United States of America
State/province [14] 0 0
Iowa
Country [15] 0 0
United States of America
State/province [15] 0 0
Kentucky
Country [16] 0 0
United States of America
State/province [16] 0 0
Louisiana
Country [17] 0 0
United States of America
State/province [17] 0 0
Maine
Country [18] 0 0
United States of America
State/province [18] 0 0
Maryland
Country [19] 0 0
United States of America
State/province [19] 0 0
Massachusetts
Country [20] 0 0
United States of America
State/province [20] 0 0
Michigan
Country [21] 0 0
United States of America
State/province [21] 0 0
Minnesota
Country [22] 0 0
United States of America
State/province [22] 0 0
Mississippi
Country [23] 0 0
United States of America
State/province [23] 0 0
Missouri
Country [24] 0 0
United States of America
State/province [24] 0 0
Nebraska
Country [25] 0 0
United States of America
State/province [25] 0 0
Nevada
Country [26] 0 0
United States of America
State/province [26] 0 0
New Hampshire
Country [27] 0 0
United States of America
State/province [27] 0 0
New Jersey
Country [28] 0 0
United States of America
State/province [28] 0 0
New Mexico
Country [29] 0 0
United States of America
State/province [29] 0 0
New York
Country [30] 0 0
United States of America
State/province [30] 0 0
North Carolina
Country [31] 0 0
United States of America
State/province [31] 0 0
North Dakota
Country [32] 0 0
United States of America
State/province [32] 0 0
Ohio
Country [33] 0 0
United States of America
State/province [33] 0 0
Oklahoma
Country [34] 0 0
United States of America
State/province [34] 0 0
Oregon
Country [35] 0 0
United States of America
State/province [35] 0 0
Pennsylvania
Country [36] 0 0
United States of America
State/province [36] 0 0
Rhode Island
Country [37] 0 0
United States of America
State/province [37] 0 0
South Carolina
Country [38] 0 0
United States of America
State/province [38] 0 0
South Dakota
Country [39] 0 0
United States of America
State/province [39] 0 0
Tennessee
Country [40] 0 0
United States of America
State/province [40] 0 0
Texas
Country [41] 0 0
United States of America
State/province [41] 0 0
Utah
Country [42] 0 0
United States of America
State/province [42] 0 0
Vermont
Country [43] 0 0
United States of America
State/province [43] 0 0
Virginia
Country [44] 0 0
United States of America
State/province [44] 0 0
Washington
Country [45] 0 0
United States of America
State/province [45] 0 0
West Virginia
Country [46] 0 0
United States of America
State/province [46] 0 0
Wisconsin
Country [47] 0 0
Canada
State/province [47] 0 0
Alberta
Country [48] 0 0
Canada
State/province [48] 0 0
British Columbia
Country [49] 0 0
Canada
State/province [49] 0 0
Manitoba
Country [50] 0 0
Canada
State/province [50] 0 0
Newfoundland and Labrador
Country [51] 0 0
Canada
State/province [51] 0 0
Nova Scotia
Country [52] 0 0
Canada
State/province [52] 0 0
Ontario
Country [53] 0 0
Canada
State/province [53] 0 0
Quebec
Country [54] 0 0
Canada
State/province [54] 0 0
Saskatchewan
Country [55] 0 0
Netherlands
State/province [55] 0 0
Utrecht
Country [56] 0 0
New Zealand
State/province [56] 0 0
Auckland
Country [57] 0 0
New Zealand
State/province [57] 0 0
Christchurch
Country [58] 0 0
Puerto Rico
State/province [58] 0 0
San Juan
Country [59] 0 0
Switzerland
State/province [59] 0 0
Bern
Country [60] 0 0
Switzerland
State/province [60] 0 0
Geneva
Country [61] 0 0
Switzerland
State/province [61] 0 0
Lausanne

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00085735
Trial related presentations / publications
Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy KK, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, Booth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy With Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma. J Clin Oncol. 2021 Aug 20;39(24):2685-2697. doi: 10.1200/JCO.20.02730. Epub 2021 Jun 10.
Public notes

Contacts
Principal investigator
Name 0 0
Jeff M Michalski
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00085735