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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT00085735
Ethics application status
Date submitted
14/06/2004
Date registered
16/06/2004
Date last updated
19/03/2019

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:
Untreated Childhood 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) - EFS was defined as the time interval from date of study entry to date of disease progression, disease recurrence, second malignant neoplasm or death from any cause, whichever occurs first, or to the date of last follow-up for patients without events. EFS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% CI's.
Timepoint [1] 0 0
3 years
Secondary outcome [1] 0 0
Overall Survival (OS) - OS was defined as the time interval from date of study entry to date of death from any cause or to the date of last follow-up for survivors. OS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% CI's. For purposes of this analysis, arms I, III and V [IFRT] are combined and compared to arms II, IV and VI [PFRT].
Timepoint [1] 0 0
3 years
Secondary outcome [2] 0 0
Local Posterior Fossa (LPF) Failure Rate - LPF failure was defined as tumor recurrence/progression within the tumor bed. The cumulative incidence (CI) of LPF failure was estimated; 3-year estimates were reported with 95% confidence intervals. Patients with other failure types (e.g., NPF) and with other events prior to LPF failure (e.g., death, second malignancy) were considered as having competing events.
Timepoint [2] 0 0
3 years
Secondary outcome [3] 0 0
Non-local Posterior Fossa (NLPF) Failure Rate - NLPF failure was defined as tumor recurrence/progression outside the radiation therapy clinical target volume boost (CTV-boost) but within the posterior fossa CTV (CTV-PF). The cumulative incidence (CI) of NLPF failure was estimated; 3-year estimates were reported with 95% confidence intervals. Patients with other failure types (e.g., NPF, LPF) and with other events prior to NLPF failure (e.g., death, second malignancy) were considered as having competing events.
Timepoint [3] 0 0
3 years
Secondary outcome [4] 0 0
Non-posterior Fossa (NPF) Failure Rate - NPF failure was defined as tumor recurrence within the neuroaxis but outside the radiation therapy clinical target volume (CTV). The cumulative incidence (CI) of NPF failure was estimated; 3-year estimates were reported with 95% confidence intervals. Patients with other failure types (e.g., LPF failure) and with other events prior to NPF failure (e.g., death, second malignancy) were considered as having competing events.
Timepoint [4] 0 0
3 years
Secondary outcome [5] 0 0
Post-treatment Endocrine Function as Measured by Thyroid Stimulating Hormone (TSH) by CSI Group - Thyroid stimulating hormone (TSH) was measured by laboratory assessment.
Timepoint [5] 0 0
Post-treatment- Up to 3 years
Secondary outcome [6] 0 0
Post-treatment Grade 3+ Hearing Loss as Measured by CTCAE v4 - 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.
Timepoint [6] 0 0
Up to 1 year after the end of treatment
Secondary outcome [7] 0 0
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) - 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.
Timepoint [7] 0 0
6 years post-diagnosis
Secondary outcome [8] 0 0
Incidence of Grade 3+ Hearing Loss at 1-year Post Treatment as Assessed by CTCAE Version 4 - Proportions of pts with grade 3+ hearing impairment as assessed by CTCAE v4 at 1-year post treatment were calculated.
Timepoint [8] 0 0
1 year after end of treatment
Secondary outcome [9] 0 0
Incidence of Endocrine Dysfunction as Measured by Growth Hormone Stimulation Tests at the Time of Completion of Therapy by RT Group - Endocrine dysfunction was assessed by growth hormone stimulation (GHS) tests. We report the percentage of patients with abnormal growth hormone stimulation tests although data were very limited.
Timepoint [9] 0 0
At end of treatment
Secondary outcome [10] 0 0
Overall Survival (OS) by Molecular Subgroup Based on Methylation Arrays - OS was defined as the time interval from date of study entry to date of death from any cause or to date of last contact for survivors. OS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% CI's.
Timepoint [10] 0 0
3 years
Secondary outcome [11] 0 0
Progression-free Survival (PFS) by Molecular Subgroup Based on Methylation Arrays - PFS was defined as the time interval from date of study entry to disease progression, relapse or death due to cancer or to last follow-up. Second malignancies and deaths from causes clearly not associated with tumor progression or recurrence were censored. PFS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% CI's.
Timepoint [11] 0 0
3 years
Secondary outcome [12] 0 0
Compliance Rates for All Eligible and Evaluable Patients Enrolled - 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.
Timepoint [12] 0 0
6 years 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
Gender
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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Den Haag
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
Switzerland
State/province [58] 0 0
Bern
Country [59] 0 0
Switzerland
State/province [59] 0 0
Geneva
Country [60] 0 0
Switzerland
State/province [60] 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/show/NCT00085735
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jeff 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
Other publications