The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00392327




Registration number
NCT00392327
Ethics application status
Date submitted
25/10/2006
Date registered
26/10/2006
Date last updated
26/01/2024

Titles & IDs
Public title
Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Previously Untreated, High-Risk Medulloblastoma/PNET
Scientific title
Efficacy of Carboplatin Administered Concomitantly With Radiation and Isotretinoin as a Pro-Apoptotic Agent in Other Than Average Risk Medulloblastoma/PNET Patients
Secondary ID [1] 0 0
NCI-2009-00336
Secondary ID [2] 0 0
ACNS0332
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
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 - Carboplatin
Treatment: Drugs - Cisplatin
Treatment: Drugs - Cyclophosphamide
Treatment: Other - Filgrastim
Treatment: Drugs - Isotretinoin
Other interventions - Laboratory Biomarker Analysis
Other interventions - Quality-of-Life Assessment
Treatment: Other - Radiation Therapy
Treatment: Drugs - Vincristine Sulfate

Active comparator: Arm A (chemoradiotherapy) - CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.

MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days).

Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.

Experimental: Arm B (chemoradiotherapy) - CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.

MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A.

Experimental: Arm C (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL) - CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm A. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.

MAINTENANCE THERAPY: Patients receive isotretinoin PO BID on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm A maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Experimental: Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL) - CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.

MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C.


Treatment: Drugs: Carboplatin
Given IV

Treatment: Drugs: Cisplatin
Given IV

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Other: Filgrastim
Given IV or SC

Treatment: Drugs: Isotretinoin
Given PO

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Other interventions: Quality-of-Life Assessment
Ancillary studies

Treatment: Other: Radiation Therapy
Undergo 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
Percent Probability of Event-free Survival (EFS) for Patients With Medulloblastoma
Timepoint [1] 0 0
Up to 5 years
Primary outcome [2] 0 0
Percent Probability of Event-free Survival (EFS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [1] 0 0
Tumor Response to Radiation Therapy for Patients With Medulloblastoma
Timepoint [1] 0 0
12 weeks after treatment initiation
Secondary outcome [2] 0 0
Tumor Response to Radiation Therapy for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)
Timepoint [2] 0 0
12 weeks after treatment initiation
Secondary outcome [3] 0 0
Percent Probability of Overall Survival (OS) for Patients With Medulloblastoma
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
Percent Probability of Overall Survival (OS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients
Timepoint [5] 0 0
6 - 12 months post diagnosis
Secondary outcome [6] 0 0
The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for Medulloblastoma Patients
Timepoint [6] 0 0
24 - 36 months post diagnosis
Secondary outcome [7] 0 0
The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for Medulloblastoma Patients
Timepoint [7] 0 0
48 - 72 months post diagnosis
Secondary outcome [8] 0 0
The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for SPNET Patients
Timepoint [8] 0 0
6 - 12 months post diagnosis
Secondary outcome [9] 0 0
The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for SPNET Patients
Timepoint [9] 0 0
24 - 36 months post diagnosis
Secondary outcome [10] 0 0
The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for SPNET Patients
Timepoint [10] 0 0
48 - 72 months post diagnosis
Secondary outcome [11] 0 0
Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients
Timepoint [11] 0 0
6 - 12 months post diagnosis
Secondary outcome [12] 0 0
Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for Medulloblastoma Patients
Timepoint [12] 0 0
24 - 36 months post diagnosis
Secondary outcome [13] 0 0
Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for Medulloblastoma Patients
Timepoint [13] 0 0
48 - 72 months post diagnosis
Secondary outcome [14] 0 0
Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for SPNET Patients
Timepoint [14] 0 0
6 - 12 months post diagnosis
Secondary outcome [15] 0 0
Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for SPNET Patients
Timepoint [15] 0 0
24 - 36 months post diagnosis
Secondary outcome [16] 0 0
Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for SPNET Patients
Timepoint [16] 0 0
48 - 72 months post diagnosis

Eligibility
Key inclusion criteria
* Newly diagnosed, previously untreated: (1) M0 medulloblastoma with > 1.5 cm^2 residual; (2) M+ medulloblastoma; patients with diffusely anaplastic medulloblastoma are eligible regardless of M-stage or residual tumor

* As of amendment # 2, enrollment of patients with supratentorial PNET has been discontinued
* All patients with M4 disease are not eligible
* A pre-operative magnetic resonance imaging (MRI) scan of the brain with and without contrast is required; NOTE: computed tomography (CT) scans are NOT sufficient for study eligibility

* Post-operative head MRI scan with and without contrast (preferably within 72 hours post-surgery); for patients who undergo stereotactic biopsy only, either a pre or post-operative MRI is sufficient; for patients with M2 and M3 disease, a post-op MRI is strongly encouraged, but not mandatory
* Spinal MRI imaging with and without gadolinium is required within 10 days of surgery if done pre-operatively or within 28 days of surgery if done post-operatively; for posterior fossa tumors, pre-operative MRI scans are preferred
* Lumbar cerebrospinal fluid (CSF) cytology examination must be obtained pre-operatively or within 31 days following surgery; the optimal time for obtaining CSF is prior to surgery or 1-3 weeks following surgery; ventricular CSF (either pre- or post-op) may be used only if a post-operative spinal tap is contraindicated; if a spinal tap is contraindicated and there is no ventricular CSF available, then CSF cytology can be waived for patients with supratentorial tumors or if there is documentation of spinal subarachnoid metastases (M3); patients who are categorized as M1 must have either an intra-operative positive CSF (via lumbar puncture at the end of the procedure) or a positive lumbar CSF obtained > 7 days post-operatively
* Patients must have a Karnofsky performance level of >= 30 for patients > 16 years of age or a Lansky performance scale of >= 30 for patients =< 16 years of age and life expectancy > 8 weeks
* No previous chemotherapy or radiation therapy
* Corticosteroids should not be used during chemotherapy administration as an antiemetic
* Selected strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (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 (vincristine sulfate)
* CYP450 3A4 stimulators or inhibitors should be avoided or used with great caution when taking cyclophosphamide; aprepitant should also be used with caution with etoposide or vincristine chemotherapy
* Cisplatin should be used with caution with nephrotoxic drug; aminoglycoside should be avoided or used with caution during or shortly after cisplatin administration and concomitant use with amphotericin B should probably also be avoided; patients receiving cisplatin and other potentially ototoxic drugs such as aminoglycoside or loop diuretics concomitantly should be closely monitored for signs of ototoxicity

* Plasma levels of anticonvulsant agents should be monitored and doses adjusted during therapy with cisplatin
* No other experimental therapy is permitted while on study
* 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:

* 0.8 mg/dL (2 to < 6 years of age)
* 1.0 mg/dL (6 to < 10 years of age)
* 1.2 mg/dL (10 to < 13 years of age)
* 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
* 1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)
* Total bilirubin < 1.5 x upper limit of normal (ULN) for age
* Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age; for patients on anti-seizure medications, SGOT (AST) or SGPT (ALT) must be < 5 x ULN
* Absolute neutrophil count (ANC) >= 1,000/uL
* Platelets >= 100,000/uL (untransfused)
* Hemoglobin >= 8 g/dl (may be transfused)
* Female patients who are post-menarchal must have a negative pregnancy test; lactating female patients must agree not to breast-feed while on this trial; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
* 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
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
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
Alaska
Country [3] 0 0
United States of America
State/province [3] 0 0
Arizona
Country [4] 0 0
United States of America
State/province [4] 0 0
Arkansas
Country [5] 0 0
United States of America
State/province [5] 0 0
California
Country [6] 0 0
United States of America
State/province [6] 0 0
Colorado
Country [7] 0 0
United States of America
State/province [7] 0 0
Connecticut
Country [8] 0 0
United States of America
State/province [8] 0 0
Delaware
Country [9] 0 0
United States of America
State/province [9] 0 0
District of Columbia
Country [10] 0 0
United States of America
State/province [10] 0 0
Florida
Country [11] 0 0
United States of America
State/province [11] 0 0
Georgia
Country [12] 0 0
United States of America
State/province [12] 0 0
Hawaii
Country [13] 0 0
United States of America
State/province [13] 0 0
Idaho
Country [14] 0 0
United States of America
State/province [14] 0 0
Illinois
Country [15] 0 0
United States of America
State/province [15] 0 0
Indiana
Country [16] 0 0
United States of America
State/province [16] 0 0
Iowa
Country [17] 0 0
United States of America
State/province [17] 0 0
Kentucky
Country [18] 0 0
United States of America
State/province [18] 0 0
Louisiana
Country [19] 0 0
United States of America
State/province [19] 0 0
Maine
Country [20] 0 0
United States of America
State/province [20] 0 0
Maryland
Country [21] 0 0
United States of America
State/province [21] 0 0
Massachusetts
Country [22] 0 0
United States of America
State/province [22] 0 0
Michigan
Country [23] 0 0
United States of America
State/province [23] 0 0
Minnesota
Country [24] 0 0
United States of America
State/province [24] 0 0
Mississippi
Country [25] 0 0
United States of America
State/province [25] 0 0
Missouri
Country [26] 0 0
United States of America
State/province [26] 0 0
Nebraska
Country [27] 0 0
United States of America
State/province [27] 0 0
Nevada
Country [28] 0 0
United States of America
State/province [28] 0 0
New Hampshire
Country [29] 0 0
United States of America
State/province [29] 0 0
New Jersey
Country [30] 0 0
United States of America
State/province [30] 0 0
New Mexico
Country [31] 0 0
United States of America
State/province [31] 0 0
New York
Country [32] 0 0
United States of America
State/province [32] 0 0
North Carolina
Country [33] 0 0
United States of America
State/province [33] 0 0
North Dakota
Country [34] 0 0
United States of America
State/province [34] 0 0
Ohio
Country [35] 0 0
United States of America
State/province [35] 0 0
Oklahoma
Country [36] 0 0
United States of America
State/province [36] 0 0
Oregon
Country [37] 0 0
United States of America
State/province [37] 0 0
Pennsylvania
Country [38] 0 0
United States of America
State/province [38] 0 0
South Carolina
Country [39] 0 0
United States of America
State/province [39] 0 0
South Dakota
Country [40] 0 0
United States of America
State/province [40] 0 0
Tennessee
Country [41] 0 0
United States of America
State/province [41] 0 0
Texas
Country [42] 0 0
United States of America
State/province [42] 0 0
Utah
Country [43] 0 0
United States of America
State/province [43] 0 0
Vermont
Country [44] 0 0
United States of America
State/province [44] 0 0
Virginia
Country [45] 0 0
United States of America
State/province [45] 0 0
Washington
Country [46] 0 0
United States of America
State/province [46] 0 0
West Virginia
Country [47] 0 0
United States of America
State/province [47] 0 0
Wisconsin
Country [48] 0 0
Canada
State/province [48] 0 0
Alberta
Country [49] 0 0
Canada
State/province [49] 0 0
British Columbia
Country [50] 0 0
Canada
State/province [50] 0 0
Manitoba
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
Puerto Rico
State/province [56] 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
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
James M Olson
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?

Results publications and other study-related documents

TypeCitations or Other Details
Journal Hwang EI, Kool M, Burger PC, Capper D, Chavez L, B... [More Details]