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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/NCT00085202




Registration number
NCT00085202
Ethics application status
Date submitted
10/06/2004
Date registered
11/06/2004
Date last updated
8/02/2024

Titles & IDs
Public title
Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor
Scientific title
Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor
Secondary ID [1] 0 0
NCI-2011-01185
Secondary ID [2] 0 0
SJMB03
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Brain and Central Nervous System Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - 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
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - filgrastim
Treatment: Drugs - cisplatin
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - vincristine
Treatment: Surgery - autologous hematopoietic stem cell transplantation
Treatment: Other - radiation therapy

Experimental: Stratum 1 (high-risk group) - Patients undergo craniospinal radiotherapy once daily 5 days a week for 6 weeks. Six weeks after the completion of radiotherapy, patients receive high-dose chemotherapy followed by autologous stem cell transplantation (SCT) and filgrastim (G-CSF) with post-transplantation vincristine. High-dose chemotherapy and autologous SCT repeat every 4 weeks for 3 additional courses in the absence of unacceptable toxicity.
Interventions: vincristine, cisplatin, cyclophosphamide, autologous hematopoietic stem cell transplantation, filgrastim, radiation therapy

Experimental: Stratum 2 (average-risk group) - Patients undergo craniospinal radiotherapy as in stratum 1, but at a lower dose. Patients receive high-dose chemotherapy, autologous SCT, G-CSF, and post-transplantation vincristine as in stratum 1.
Interventions: vincristine, cisplatin, cyclophosphamide, autologous hematopoietic stem cell transplantation, filgrastim, radiation therapy


Other interventions: filgrastim
Given subcutaneously

Treatment: Drugs: cisplatin
Given IV

Treatment: Drugs: cyclophosphamide
Given IV

Treatment: Drugs: vincristine
Given IV

Treatment: Surgery: autologous hematopoietic stem cell transplantation
Patients undergo autologous stem cell transplantation

Treatment: Other: radiation therapy
Patients undergo craniospinal radiotherapy once daily 5 days a week for 6 weeks.

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
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) in ERBB2-Negative Tumors Compared to ERBB2-Positive Tumors
Timepoint [1] 0 0
2 years after tumor cell analysis in 122 participants
Primary outcome [2] 0 0
Progression-Free Survival (PFS) Compared Between ERBB2 Assessment and Risk Group.
Timepoint [2] 0 0
2 years after tumor cell analysis in 122 participants
Primary outcome [3] 0 0
Frequency of Mutations Associated With SHH and WNT Tumors
Timepoint [3] 0 0
within 3.5 years following completion of accrual
Secondary outcome [1] 0 0
Reading Decoding Composite Scores in the Intervention and Standard of Care Groups
Timepoint [1] 0 0
5 years postdiagnosis
Secondary outcome [2] 0 0
Number of Average Risk Patients Whose Treatment Failure Included the Posterior Fossa
Timepoint [2] 0 0
Annually for 6 years post irradiation
Secondary outcome [3] 0 0
Associative Memory for Two Risk Group at Enrollment
Timepoint [3] 0 0
At enrollment
Secondary outcome [4] 0 0
Associative Memory for Two Risk Group at 5 Years After Enrollment
Timepoint [4] 0 0
At 5 years after enrollment
Secondary outcome [5] 0 0
Processing Speed for Two Risk Group at Enrollment
Timepoint [5] 0 0
At enrollment
Secondary outcome [6] 0 0
Processing Speed for Two Risk Group at 5 Years After Enrollment
Timepoint [6] 0 0
At 5 years after enrollment
Secondary outcome [7] 0 0
Perceptual Speed for Two Risk Group at Enrollment
Timepoint [7] 0 0
At enrollment
Secondary outcome [8] 0 0
Perceptual Speed for Two Risk Group at 5 Years After Enrollment
Timepoint [8] 0 0
At 5 years after enrollment

Eligibility
Key inclusion criteria
DISEASE CHARACTERISTICS:

- Histologically confirmed diagnosis of 1 of the following:

- Medulloblastoma

- Supratentorial primitive neuroectodermal tumor (PNET)

- PNET variants (ependymoblastoma, pineoblastoma, CNS neuroblastoma)

- Atypical teratoid rhabdoid tumor (ATRT)

- Definitive surgery for CNS tumor within the past 31 days

- Meets one of the following risk criteria:

- Average-risk disease

- Localized disease with no overt evidence of invasion beyond the posterior
fossa (or supratentorial compartment for PNET or ATRT) by intraoperative
observations of the neurosurgeon AND postoperative CT scan or MRI

- T4 disease eligible if all of the following are true:

- Gross total resection determined by intraoperative observations of the
neurosurgeon AND postoperative CT scan or MRI

- Residual tumor or imaging abnormality whose size is < 1.5 cm^2

- No evidence of CNS or extraneural metastasis by MRI of the spine (with
and without contrast agent) or CT-based myelogram AND by cytologic
examination of the lumbar cerebral spinal fluid (CSF) 14-28 days after
surgery

- Brain stem invasion allowed in the absence of residual tumor (tumor < 1.5
cm^2 by imaging)

- High-risk disease meeting one of the following criteria:

- Metastatic disease within the neuraxis (i.e., evidence of subarachnoid
dissemination by imaging and/or cytologic examination of CSF)

- Presence of residual disease > 1.5 cm^2 at the primary site after surgery

PATIENT CHARACTERISTICS:

Age

- 3 to 21 at diagnosis

Performance status

- Lansky 30-100% (< 10 years old)

- Karnofsky 30-100% (= 10 years old) (except for posterior fossa syndrome)

Life expectancy

- Not specified

Hematopoietic

- Hemoglobin > 8 g/dL

- WBC > 2,000/mm^3

- Absolute neutrophil count > 500/mm^3

- Platelet count > 50,000/mm^3

Hepatic

- ALT < 5 times normal

- Bilirubin < 3.0 mg/dL

Renal

- Creatinine < 2.0 mg/dL OR

- Creatinine clearance > 70 mL/min

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- No prior chemotherapy

Endocrine therapy

- Prior corticosteroid therapy allowed

Radiotherapy

- No prior radiotherapy

Surgery

- See Disease Characteristics
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
Non-randomised 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)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Lady Cilento Children's Hospital, Brisbane - Brisbane
Recruitment hospital [4] 0 0
Royal Children's Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4029 - Brisbane
Recruitment postcode(s) [4] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
North Carolina
Country [2] 0 0
United States of America
State/province [2] 0 0
Pennsylvania
Country [3] 0 0
United States of America
State/province [3] 0 0
Tennessee
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Other
Name
St. Jude Children's Research Hospital
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Drugs used in chemotherapy, such as vincristine, cisplatin, and cyclophosphamide, work in
different ways to stop tumor cells from dividing so they stop growing or die. Radiation
therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with
chemotherapy may kill more tumor cells. Autologous stem cell transplant may be able to
replace blood-forming cells that were destroyed by chemotherapy or radiation therapy. It is
not yet known which radiation therapy regimen combined with chemotherapy and donor stem cell
transplant is more effective in treating medulloblastoma, supratentorial primitive
neuroectodermal tumor, or atypical teratoid rhabdoid tumor.

This phase III trial is studying two different regimens of radiation therapy when given
together with chemotherapy and autologous stem cell transplant to see how well they work in
treating patients with newly diagnosed medulloblastoma, supratentorial primitive
neuroectodermal tumor, or atypical teratoid rhabdoid tumor.

PRIMARY OBJECTIVE:

- To assess the relationship between ERBB2 protein expression in tumors and
progression-free survival probability for patients with medulloblastoma.

- To estimate the frequency of mutations associated with SHH and WNT tumors (as defined by
gene expression profiling) via targeted sequencing performed in an independent cohort of
WNT and SHH tumors (also defined by gene expression profiling).
Trial website
https://clinicaltrials.gov/ct2/show/NCT00085202
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Amar Gajjar, MD
Address 0 0
St. Jude Children's Research Hospital
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/NCT00085202