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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02724579
Ethics application status
Date submitted
25/03/2016
Date registered
31/03/2016
Date last updated
15/08/2024

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: Surgery - Magnetic Resonance Imaging
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.

Patients also undergo MRI throughout the trial.


Treatment: Drugs: Cisplatin
Given IV

Treatment: Drugs: Cyclophosphamide
Given IV

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Lomustine
Given PO

Treatment: Surgery: Magnetic Resonance Imaging
Undergo MRI

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: Surgery
Intervention code [4] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS)
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
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
Timepoint [2] 0 0
Baseline to up to 60 months post-diagnosis

Eligibility
Key inclusion criteria
* Patients must be greater than or equal to 3 years and less than 22 years of age at the time of enrollment
* 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 by Sanger sequencing
* 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 >= 8.0 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
Sex
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. Children with posterior fossa syndrome (also known as cerebellar mutism) are eligible for this study

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/11/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2027
Actual
Sample size
Target
45
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [3] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment hospital [4] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
5006 - North Adelaide
Recruitment postcode(s) [3] 0 0
6008 - Perth
Recruitment postcode(s) [4] 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
State/province [2] 0 0
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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Maine
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Massachusetts
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Michigan
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Nebraska
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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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Alberta
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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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Ontario
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Quebec
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Saskatchewan
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Puerto Rico
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Caguas
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Puerto Rico
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San Juan
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Saudi Arabia
State/province [58] 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
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT02724579