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Trial record 1 of 1 for:    NCT00392327
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Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Previously Untreated, High-Risk Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor

This study is currently recruiting participants.
Verified June 2013 by Children's Oncology Group
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00392327
First received: October 25, 2006
Last updated: June 10, 2013
Last verified: June 2013
History of Changes
  Purpose

This randomized phase III trial is studying different chemotherapy and radiation therapy regimens to compare how well they work in treating young patients with newly diagnosed, previously untreated, high-risk medulloblastoma or supratentorial primitive neuroectodermal tumor. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Isotretinoin may help chemotherapy work better by making tumor cells more sensitive to the drugs. Radiation therapy uses high-energy x-rays to kill tumor cells. Carboplatin may make tumor cells more sensitive to radiation therapy. It is not yet known which chemotherapy and radiation therapy regimen is more effective in treating brain tumors.


Condition Intervention Phase
Untreated Childhood Medulloblastoma
Untreated Childhood Pineoblastoma
Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor
 Drug: carboplatin
Drug: cyclophosphamide
Biological: filgrastim
Drug: cisplatin
Drug: isotretinoin
Drug: vincristine sulfate
Radiation: radiation therapy
Other: laboratory biomarker analysis
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy of Carboplatin Administered Concomitantly With Radiation and Isotretinoin as a Pro-Apoptotic Agent in Other Than Average Risk Medulloblastoma/PNET Patients

Resource links provided by NLM:

MedlinePlus related topics: Cancer
U.S. FDA Resources

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event-free survival (EFS) percentage [ Time Frame: Time from disease progression or recurrence, occurrence of a second malignant neoplasm, or death from any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    Based on stratified logrank test, with stratification on all randomization stratifiers as well as on the factorial treatment group not the subject of the analysis. Good approximation to the power of these test are obtained using the methods of Sposto and Sather. Monitoring for differences in long-term EFS will be based on the same one-sided likelihood ratio test


Secondary Outcome Measures:
  • Tumor response to radiotherapy (RT) with or without carboplatin using width (W), transverse (T), and length (L) measurements [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Using a two-sided test of proportions with Type I error 5%, this sample size will provide at least 80% power to detect a 30% difference in post-RT response rate between the two treatment groups. There will be no interim monitoring based on this endpoint.

  • Time to death [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Survival (S) percentage will be computed from time to death.


Estimated Enrollment: 300
Study Start Date: March 2007
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (chemotherapy, RT, immunomodulating therapy)
Patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40 and receive vincristine IV over 1 minute on days 1, 8, 15, 22, 29, and 36. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. Patients receive cisplatin IV over 6 hours on day 1, vincristine IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive G-CSF SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days). Treatment with maintenance therapy repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.
 Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • Neupogen
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (chemotherapy, RT, immunomodulating therapy)
Patients receive carboplatin IV over 15 minutes once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40 and undergo radiotherapy and receive vincristine as in arm I. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. Patients receive maintenance therapy as in arm I.
 Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • Neupogen
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm III (chemotherapy, RT, antineoplastic therapy)
Patients undergo chemoradiotherapy as in arm I. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. Patients receive oral isotretinoin twice daily on day 1 and days 16-28 and cisplatin, vincristine, cyclophosphamide, and G-CSF as in arm I maintenance therapy. Treatment with maintenance therapy 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. Patients receive oral isotretinoin twice daily on days 15-28. Treatment with continuation therapy repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
 Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • Neupogen
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: isotretinoin
Given orally
Other Names:
  • 13-CRA
  • Amnesteem
  • Cistane
  • Claravis
  • Sotret
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm IV (chemotherapy, RT, antineoplastic therapy)
(Standard chemoradiotherapy plus carboplatin, standard maintenance therapy plus isotretinoin, and continuation therapy with isotretinoin): Patients undergo chemoradiotherapy as in arm II. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. Patients receive maintenance therapy as in arm III. Patients then proceed to continuation therapy. Patients receive continuation therapy as in arm III.
 Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • Neupogen
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: isotretinoin
Given orally
Other Names:
  • 13-CRA
  • Amnesteem
  • Cistane
  • Claravis
  • Sotret
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed diagnosis of medulloblastoma or supratentorial primitive neuroectodermal tumor (PNET)

    • Newly diagnosed disease
    • Previously untreated disease

  • Meets 1 of the following criteria:

    • M0 medulloblastoma with > 1.5 cm² residual tumor
    • M+ medulloblastoma
    • M0 or M+ supratentorial PNET (including pineoblastoma)
    • Diffusely anaplastic medulloblastoma with any M-stage or residual tumor
  • Must have undergone stereotactic biopsy or attempted neurosurgical resection of the tumor within the past 31 days

  • The following procedures are required:

    • Pre-operative MRI of the brain with and without contrast
    • Post-operative (preferably within 72 hours after surgery) MRI of the brain with and without contrast**
    • Spinal MRI with and without contrast within 10 days before surgery or 28 days after surgery
    • Lumbar cerebrospinal fluid (CSF) cytological examination obtained pre-operatively or within 31 days after surgery***
  • No M4 disease
  • Karnofsky performance status (PS) 30-100% (for patients > 16 years of age) OR Lansky PS 30-100% (for patients ≤ 16 years of age)
  • Life expectancy > 8 weeks
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use 2 effective forms of contraception

  • Creatinine normal OR creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR serum creatinine based on age and/or gender as follows:

    • 0.4 mg/dL (1 month to < 6 months of age)
    • 0.5 mg/dL (6 months to < 1 year of age)
    • 0.6 mg/dL (1 to < 2 years of age)
    • 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)
  • Bilirubin < 1.5 times upper limit of normal (ULN)
  • AST and ALT < 2.5 times ULN (5 times ULN for patients on antiseizure medications)
  • Absolute neutrophil count ≥ 1,000/mm³
  • Platelet count ≥ 100,000/mm³ (transfusions not allowed)
  • Hemoglobin ≥ 8 g/dL (transfusions allowed)
  • No concurrent corticosteroids as an antiemetic during chemotherapy
  • No prior chemotherapy or radiotherapy
  • No other concurrent experimental therapy
  • No concurrent isotretinoin for acne treatment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00392327

  Show 168 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: James Olson Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00392327     History of Changes
Other Study ID Numbers: ACNS0332, NCI-2009-00336, COG-ACNS0332, CDR0000511991, U10CA098543, R01CA114567
Study First Received: October 25, 2006
Last Updated: June 10, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Medulloblastoma
Pinealoma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Glioma
Neoplasms, Neuroepithelial
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
 Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cisplatin
Cyclophosphamide
Vincristine
Carboplatin
Lenograstim
Isotretinoin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Immunosuppressive Agents

ClinicalTrials.gov processed this record on June 13, 2013