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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00336024




Registration number
NCT00336024
Ethics application status
Date submitted
8/06/2006
Date registered
12/06/2006
Date last updated
25/09/2023

Titles & IDs
Public title
Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma
Scientific title
A Phase III Randomized Trial for the Treatment of Newly Diagnosed Supratentorial PNET and High Risk Medulloblastoma in Children < 36 Months Old With Intensive Induction Chemotherapy With Methotrexate Followed by Consolidation With Stem Cell Rescue vs. the Same Therapy Without Methotrexate
Secondary ID [1] 0 0
NCI-2009-00338
Secondary ID [2] 0 0
ACNS0334
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anaplastic Medulloblastoma 0 0
Medulloblastoma 0 0
Supratentorial Embryonal Tumor, Not Otherwise Specified 0 0
Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Children's - Brain
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Neuroendocrine tumour (NET)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Autologous Hematopoietic Stem Cell Transplantation
Treatment: Drugs - Carboplatin
Treatment: Drugs - Cisplatin
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Etoposide
Other interventions - Filgrastim
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Leucovorin Calcium
Treatment: Drugs - Methotrexate
Other interventions - Quality-of-Life Assessment
Treatment: Drugs - Thiotepa
Treatment: Drugs - Vincristine Sulfate

Active Comparator: Arm I (induction+consolidation chemotherapy, autologous PBSC) - Patients receive vincristine IV over 1 minute on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses.
Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and G-CSF IV or SC beginning on day 5 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Experimental: Arm II (induction+consolidation chemotherapy, autologous PBSC) - Patients receive vincristine IV over 1 minute on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or PO every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses.
Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and G-CSF IV or SC beginning on day 5 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.


Treatment: Surgery: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSC resuce

Treatment: Drugs: Carboplatin
Given IV

Treatment: Drugs: Cisplatin
Given IV

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Etoposide
Given IV

Other interventions: Filgrastim
Given IV or SC

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Leucovorin Calcium
Given IV or orally

Treatment: Drugs: Methotrexate
Given IV

Other interventions: Quality-of-Life Assessment
Ancillary studies

Treatment: Drugs: Thiotepa
Given IV

Treatment: Drugs: Vincristine Sulfate
Given IV

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

Outcomes
Primary outcome [1] 0 0
Number of Patients Who Have Either a Complete Response (CR) Rate or No Complete Response Rate
Timepoint [1] 0 0
At the end of consolidation treatment
Secondary outcome [1] 0 0
Number of Participants With Molecular Sub-types of MB, CNS-PNETs/EBTs Represented in the ACNS0334 Cohort
Timepoint [1] 0 0
At baseline
Secondary outcome [2] 0 0
Percentage of Participants With Event Free Survival (EFS)
Timepoint [2] 0 0
Baseline to up to 5 years
Secondary outcome [3] 0 0
Patterns of Failure
Timepoint [3] 0 0
Baseline to up to 5 years
Secondary outcome [4] 0 0
Percentage of Participants With Any Acute Adverse Events
Timepoint [4] 0 0
Beginning of treatment to the end of consolidation
Secondary outcome [5] 0 0
Number of Participants With Acute Hearing Loss and No Acute Hearing Loss
Timepoint [5] 0 0
Beginning of treatment to the end of consolidation
Secondary outcome [6] 0 0
Number of Participants With Chronic Primary Hypothyroidism/Subclinical Compensatory HypothyroidismHypothyroidism/Subclinical Compensatory Hypothyroidism
Timepoint [6] 0 0
Off-treatment up to 9 years
Secondary outcome [7] 0 0
Number of Participants With Chronic Central Hypothyroidism
Timepoint [7] 0 0
Off-treatment up to 9 years
Secondary outcome [8] 0 0
Number of Participants With Chronic Low Somatomedin C
Timepoint [8] 0 0
Off-treatment up to 9 years
Secondary outcome [9] 0 0
Number of Participants With Chronic Diabetes Insipidus
Timepoint [9] 0 0
Beginning of off-treatment to up to 9 years
Secondary outcome [10] 0 0
Number of Participants With Secondary Malignancies
Timepoint [10] 0 0
Off-treatment up to 9 years
Secondary outcome [11] 0 0
Number of Participants With Chronic/Late Hearing Loss and No Chronic/Late Hearing Loss
Timepoint [11] 0 0
Off-treatment up to 9 years
Secondary outcome [12] 0 0
Rates of Gastrointestinal Toxicities
Timepoint [12] 0 0
Beginning of treatment to the end of consolidation
Secondary outcome [13] 0 0
Rates of Nutritional Toxicities
Timepoint [13] 0 0
Beginning of treatment to the end of consolidation
Secondary outcome [14] 0 0
Median/Range of Patients for Total Quality of Life (QOL) Score, Intelligence Quotient (IQ) and Processing Speed Index (PSI).
Timepoint [14] 0 0
60 months (+/- 3 months)

Eligibility
Key inclusion criteria
- High-risk medulloblastoma defined by any of the following:

- > 1.5 cm^2 residual disease for any medulloblastoma histology, or

- Lumbar cerebral spinal fluid (CSF) cytology positive for tumor cells by analysis
of fluid collected either before definitive surgery or at least 10 days after
definitive surgery unless contraindicated, or

- Magnetic resonance imaging (MRI) evidence of M2 or M3 metastatic disease, or

- M4 disease

- Supratentorial primitive neuroectodermal tumor (PNET) (any M-stage) will be eligible
for study entry

- Children less than 8 months of age at the time of definitive surgery with or without
measurable radiographic residual tumor with M0 stage medulloblastoma will be eligible
for study entry

- Patients with anaplastic medulloblastoma are eligible regardless of M-stage or
residual tumor

- Patients with M0 classic, non-desmoplastic medulloblastoma (R1) with radiographically
measurable residual disease < 1.5 cm^2 are eligible

- Cranial MRI (with and without gadolinium) must be done pre-operatively;
post-operatively, cranial MRI (with and without gadolinium) must be done, preferably
within 48 hours of surgery; entire spinal MRI must be obtained either pre-operatively
(with gadolinium) or post-operatively (at least 10 days following surgery) prior to
study enrollment (with and without gadolinium); patients with MRI evidence of spinal
disease are eligible for this study

- Evaluation of lumbar CSF cytology (cytospin preparation for microscopic evaluation)
must be performed either pre-operatively or at least 10 days after definitive surgery
unless contraindicated

- Patient must have a life expectancy > 8 weeks

- Patient must have received no prior radiation therapy or chemotherapy other than
corticosteroids; corticosteroids are allowable for all patients

- Creatinine clearance or radioisotope glomerular filtration rate >= 60 mL/min

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

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
serum glutamic pyruvic transaminase (SGPT) (alanine transaminase [ALT]) < 2 x ULN for
age

- Shortening fraction >= 27% by echocardiogram, or

- Ejection fraction >= 47% by radionuclide angiogram

- No evidence of dyspnea at rest

- Pulse oximetry > 94% on room air

- Peripheral absolute neutrophil count (ANC) > 1,000/uL

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

- Hemoglobin greater than 8 g/dL (may have received red blood cell [RBC] transfusions
allowed)

- Hold trimethoprim/sulfamethoxazole (Bactrim) on the day of high-dose methotrexate
(HDMTX) infusion and continue to hold until the methotrexate level is less than 0.1
micromolar (1 x 10-7 M)

- Avoid probenecid, penicillins, cephalosporins, aspirin, proton pump inhibitors and
nonsteroidal anti-inflammatory drug (NSAIDS) on the day of methotrexate and continue
until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M) as renal
excretion of methotrexate is inhibited by these agents

- Avoid IV contrast media, urinary acidifiers, phenytoin, and fosphenytoin on the day of
methotrexate and until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M)

- Concurrent use of enzyme inducing anticonvulsants (e.g. phenytoin, phenobarbital, and
carbamazepine) should be avoided

- Clinically significant drug interactions have been reported when using vincristine
with strong cytochrome P450 (CYP450) family 3 subfamily A member 4 (3A4) inhibitors
and inducers; selected strong inhibitors of cytochrome P450 3A4 include azole
antifungals, such as fluconazole, voriconazole, itraconazole, ketoconazole, and strong
inducers include drugs such as rifampin, phenytoin, phenobarbitol, carbamazepine, and
St. John's wort; the use of these drugs should be avoided with vincristine

- All patients and/or their parents or legal guardians must sign a written informed
consent

- All institutional, Food and Drug administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Minimum age
No limit
Maximum age
2 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
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)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [4] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
3052 - Parkville
Recruitment postcode(s) [4] 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
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Delaware
Country [8] 0 0
United States of America
State/province [8] 0 0
District of Columbia
Country [9] 0 0
United States of America
State/province [9] 0 0
Florida
Country [10] 0 0
United States of America
State/province [10] 0 0
Georgia
Country [11] 0 0
United States of America
State/province [11] 0 0
Hawaii
Country [12] 0 0
United States of America
State/province [12] 0 0
Idaho
Country [13] 0 0
United States of America
State/province [13] 0 0
Illinois
Country [14] 0 0
United States of America
State/province [14] 0 0
Indiana
Country [15] 0 0
United States of America
State/province [15] 0 0
Iowa
Country [16] 0 0
United States of America
State/province [16] 0 0
Kentucky
Country [17] 0 0
United States of America
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Louisiana
Country [18] 0 0
United States of America
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Maine
Country [19] 0 0
United States of America
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Maryland
Country [20] 0 0
United States of America
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Massachusetts
Country [21] 0 0
United States of America
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Michigan
Country [22] 0 0
United States of America
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Minnesota
Country [23] 0 0
United States of America
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Mississippi
Country [24] 0 0
United States of America
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Missouri
Country [25] 0 0
United States of America
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Nevada
Country [26] 0 0
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New Jersey
Country [27] 0 0
United States of America
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New Mexico
Country [28] 0 0
United States of America
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New York
Country [29] 0 0
United States of America
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North Carolina
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United States of America
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North Dakota
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United States of America
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Ohio
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United States of America
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Oklahoma
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United States of America
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Oregon
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United States of America
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Pennsylvania
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United States of America
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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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United States of America
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Wisconsin
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Canada
State/province [44] 0 0
Alberta
Country [45] 0 0
Canada
State/province [45] 0 0
British Columbia
Country [46] 0 0
Canada
State/province [46] 0 0
Manitoba
Country [47] 0 0
Canada
State/province [47] 0 0
Nova Scotia
Country [48] 0 0
Canada
State/province [48] 0 0
Ontario
Country [49] 0 0
Canada
State/province [49] 0 0
Quebec
Country [50] 0 0
Puerto Rico
State/province [50] 0 0
San Juan

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 two different combination chemotherapy regimens
to compare how well they work in treating young patients with newly diagnosed supratentorial
primitive neuroectodermal tumors or high-risk medulloblastoma when given before additional
intense chemotherapy followed by peripheral blood stem cell rescue. It is not yet known which
combination chemotherapy regimen is more effective when given before a peripheral stem cell
transplant in treating supratentorial primitive neuroectodermal tumors or medulloblastoma.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00336024
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Claire M Mazewski
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/ct2/show/NCT00336024