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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02724579




Registration number
NCT02724579
Ethics application status
Date submitted
25/03/2016
Date registered
31/03/2016
Date last updated
11/06/2020

Titles & IDs
Public title
Reduced Craniospinal Radiation Therapy and Chemotherapy in Treating Younger Patients With Newly Diagnosed WNT-Driven Medulloblastoma
Scientific title
A Phase 2 Study of Reduced Therapy for Newly Diagnosed Average-Risk WNT-Driven Medulloblastoma Patients
Secondary ID [1] 0 0
NCI-2016-00150
Secondary ID [2] 0 0
ACNS1422
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: Drugs - Cyclophosphamide
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Lomustine
Treatment: Other - Radiation Therapy
Treatment: Drugs - Vincristine
Treatment: Drugs - Vincristine Sulfate

Experimental: Treatment (reduced radiation therapy and chemotherapy) - RADIATION THERAPY: Beginning 4-5 weeks after surgery, patients undergo craniospinal radiation therapy 5 days a week for 6 weeks.
MAINTENANCE THERAPY (WEEKS 1, 3, 5, and 7): Beginning 4-6 weeks after completion of radiation therapy patients receive lomustine PO on day 1, vincristine sulfate IV over 1 minute or via minibag on days 1, 8, and 15, and cisplatin IV over 6 hours on day 1. Treatment repeats every 42 days in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY (WEEKS 2, 4, AND 6): Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 2, mesna IV over 15-30 minutes on days 1 and 2, and vincristine sulfate IV over 1 minute or via minibag on days 1 and 8. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.


Treatment: Drugs: Cisplatin
Given IV

Treatment: Drugs: Cyclophosphamide
Given IV

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Lomustine
Given PO

Treatment: Other: Radiation Therapy
Undergo craniospinal radiation therapy

Treatment: Drugs: Vincristine
Given IV or via minibag

Treatment: Drugs: Vincristine Sulfate
Given IV or via minibag

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

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS) - PFS along with the confidence intervals will be estimated using the Kaplan-Meier method. PFS will also be reported based on central radiology review.
Timepoint [1] 0 0
From the initiation of protocol treatment to the occurrence of any of the following events: disease progression or disease recurrence or death from any cause, assessed up to 10 years
Secondary outcome [1] 0 0
Deoxyribonucleic acid (DNA) methylation profiling as real-time classification of WNT-driven medulloblastoma - Results will be compared to the results of the molecular screening tests. The sensitivity and specificity comparison between DNA methylation arrays and the standard methods (molecular screening tests for WNT using immunohistochemistry [IHC] and CTNNB1 sequencing) will be performed using McNemar's test.
Timepoint [1] 0 0
Within 32 days of definitive surgery
Secondary outcome [2] 0 0
Change in neurocognitive function (cognitive, social, emotional and behavioral) according to Children Oncology Group Standard Neuropsychological Battery - Neurocognitive function will be measured at 9, 30 and 60 months post diagnosis and will be compared with the neurocognitive outcomes from an age and gender matched ACNS0331 cohort to the WNT patients treated on ACNS1422. Data for all assessments will be available as standardized t-scores. The change over time for each component of the neuropsychological testing will be estimated using the Generalized Estimating Equation (GEE) approach, with the standardized t-scores as the dependent variable and the assessment times as a covariate. Within the ACNS1422 cohort GEE models will also be used to explore associations of changes over time with factors such as gender, age at initiation of radiation therapy, tumor location, number of surgical interventions, etc.
Timepoint [2] 0 0
Baseline to up to 60 months post-diagnosis

Eligibility
Key inclusion criteria
- Patients must be newly diagnosed and have:

- Eligibility confirmed by rapid central pathology and molecular screening review
on APEC14B1:

- Classical histologic type (non LC/A) WNT medulloblastoma

- Positive nuclear beta-catenin by immunohistochemistry (IHC)

- Positive for CTNNB1 mutation

- Negative for MYC and MYCN by fluorescence in situ hybridization (FISH)

- Patient must have negative lumbar cerebrospinal fluid (CSF) cytology

- Note: CSF cytology for staging should be performed no sooner than 14 days post
operatively to avoid false positive CSF; ideally, CSF should be obtained between
day 14 and day 21 to allow for final staging status before enrollment onto the
study; patients with positive CSF cytology obtained 0 to 14 days after surgery
should have cytology repeated to determine eligibility and final CSF status;
patients with negative CSF cytology from lumbar puncture obtained 0 to 14 days
after surgery do not need cytology repeated; patients with negative CSF cytology
from lumbar puncture obtained prior to surgery do not need cytology repeated
post-operatively

- Patients must have eligibility confirmed by Rapid Central Imaging Review on APEC14B1;
patients must have =< 1.5 cm^2 maximal cross-sectional area of residual tumor; whole
brain magnetic resonance imaging (MRI) with and without gadolinium and spine MRI with
gadolinium must be performed

- Patients must be enrolled, and protocol therapy must be projected to begin, no later
than 36 days after definitive diagnostic surgery (day 0)

- Peripheral absolute neutrophil count (ANC) >= 1000/uL

- Platelet count >= 100,000/uL (transfusion independent)

- Hemoglobin >= 10.0 g/dL (may receive red blood cell [RBC] transfusions)

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

- 3 to < 6 years of age: maximum (max) serum creatinine 0.8 mg/dL (males and
females)

- 6 to < 10 years of age: max serum creatinine 1 mg/dL (males and females)

- 10 to < 13 years of age: max serum creatinine 1.2 mg/dL (males and females)

- 13 to < 16 years of age: max serum creatinine 1.5 md/dL (males) and 1.4 md/dL
(females)

- >= 16 years of age: max serum creatinine 1.7 mg/dL (males) and 1.4 mg/dL
(females)

- The threshold creatinine values were derived from the Schwartz formula for
estimating GFR utilizing child length and stature data published by the
Centers for Disease Control and Prevention (CDC)

- Total or direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and

- Serum glutamate pyruvate (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (3x ULN);
for the purpose of this study, the ULN for SGPT is 45 U/L

- Central nervous system function defined as:

- Patients with seizure disorder may be enrolled if on anticonvulsants and well
controlled

- Patients must not be in status epilepticus, a coma or on assisted ventilation at
the time of study enrollment

- Patients must have receptive and expressive language skills in English, French, or
Spanish to complete the QoL and neurocognitive assessments; if a patient meets these
criteria but the parent/guardian speaks a language other than English, French, or
Spanish, the patient may still be enrolled and tested, and the parent-report measures
should be omitted

- All patients and/or their parents or legal guardians must sign a written informed
consent; assent, when appropriate, will be obtained according to institutional
guidelines

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Minimum age
3 Years
Maximum age
21 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar
CSF cytology are not eligible; patients who are unable to undergo a lumbar puncture
for assessment of CSF cytology are ineligible

- Patients must not have received any prior radiation therapy or chemotherapy
(tumor-directed therapy) other than surgical intervention and/or corticosteroids

- Pregnancy and Breast Feeding

- Female patients who are pregnant are ineligible due to risks of fetal and
teratogenic adverse events as seen in animal/human studies

- Lactating females are not eligible unless they have agreed not to breastfeed
their infants

- Female patients of childbearing potential are not eligible unless a negative
pregnancy test result has been obtained

- Sexually active patients of reproductive potential are not eligible unless they
have agreed to use an effective contraceptive method for the duration of their
study participation

- Patients with a history of moderate to profound intellectual disability (i.e.,
intelligence quotient [Q)]=< 55) are not eligible for enrollment; PLEASE NOTE:
Children with a prior history of attention deficit hyperactivity disorder (ADHD) or a
specific learning disability (e.g., dyslexia) are eligible for this study

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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 hospital [3] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
5006 - North Adelaide
Recruitment postcode(s) [2] 0 0
6008 - Perth
Recruitment postcode(s) [3] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Alaska
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Arizona
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Arkansas
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California
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Colorado
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Connecticut
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Delaware
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District of Columbia
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Florida
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Georgia
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Hawaii
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Idaho
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Illinois
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Indiana
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Iowa
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Kentucky
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Missouri
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Nebraska
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Nevada
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New Hampshire
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New Jersey
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New York
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North Carolina
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North Dakota
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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South Dakota
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Tennessee
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Texas
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Utah
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Vermont
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Virginia
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Washington
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West Virginia
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Wisconsin
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Canada
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British Columbia
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Canada
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Manitoba
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Canada
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Newfoundland and Labrador
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Canada
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Nova Scotia
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Canada
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Ontario
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Canada
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Quebec
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Canada
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Saskatchewan
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Puerto Rico
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Caguas
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Saudi Arabia
State/province [56] 0 0
Riyadh

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 phase II trial studies how well reduced doses of radiation therapy to the brain and
spine (craniospinal) and chemotherapy work in treating patients with newly diagnosed type of
brain tumor called WNT)/Wingless (WNT)-driven medulloblastoma. Recent studies using
chemotherapy and radiation therapy have been shown to be effective in treating patients with
WNT-driven medulloblastoma. However, there is a concern about the late side effects of
treatment, such as learning difficulties, lower amounts of hormones, or other problems in
performing daily activities. Radiotherapy uses high-energy radiation from x-rays to kill
cancer cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, vincristine
sulfate, cyclophosphamide and lomustine, work in different ways to stop the growth of tumor
cells, either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. Giving reduced craniospinal radiation therapy and chemotherapy may kill tumor
cells and may also reduce the late side effects of treatment.
Trial website
https://clinicaltrials.gov/show/NCT02724579
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Nicholas J Gottardo
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/show/NCT02724579