Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Previously Untreated, High-Risk Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor

This study has suspended participant recruitment.
(Temporarily Closed to Accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00392327
First received: October 25, 2006
Last updated: February 20, 2014
Last verified: February 2014

October 25, 2006
February 20, 2014
March 2007
December 2012   (final data collection date for primary outcome measure)
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
Not Provided
Complete list of historical versions of study NCT00392327 on ClinicalTrials.gov Archive Site
  • 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.
Not Provided
Not Provided
Not Provided
 
Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Previously Untreated, High-Risk Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor
Efficacy of Carboplatin Administered Concomitantly With Radiation and Isotretinoin as a Pro-Apoptotic Agent in Other Than Average Risk Medulloblastoma/PNET Patients

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.

PRIMARY OBJECTIVES:

I. Determine whether carboplatin radiosensitization increases long-term, event-free survival of pediatric patients with newly diagnosed, previously untreated, high-risk medulloblastoma or supratentorial primitive neuroectodermal tumors.

II. Determine whether isotretinoin increases long-term, event-free survival of these patients.

SECONDARY OBJECTIVES:

I. Compare residual disease response to radiotherapy alone versus radiotherapy and carboplatin in these patients.

II. Identify molecular prognostic indicators suitable for patient stratification in future trials.

OUTLINE: This is a randomized, open-label, factorial-designed, multicenter study. Patients are stratified according to location of disease and dissemination status (M0 medulloblastoma with > 1.5 cm² residual tumor vs M+ medulloblastoma vs M0 supratentorial primitive neuroectodermal tumor [SPNET] with < 1.5 cm² residual tumor vs M0 SPNET with > 1.5 cm² residual tumor vs M+ SPNET vs M0 diffusely anaplastic medulloblastoma). Patients are randomized to 1 of 4 treatment arms.

ARM I (standard chemoradiotherapy and standard maintenance therapy):

CHEMOTHERAPY: 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.

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 filgrastim (G-CSF) subcutaneously (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.

ARM II (standard chemoradiotherapy plus carboplatin and standard maintenance therapy):

CHEMORADIOTHERAPY: 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.

MAINTENANCE THERAPY: Patients receive maintenance therapy as in arm I.

ARM III (standard chemoradiotherapy, standard maintenance therapy plus isotretinoin, and continuation therapy with isotretinoin):

CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in arm I. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.

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 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 oral isotretinoin twice daily on days 15-28.

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

ARM IV (standard chemoradiotherapy plus carboplatin, standard maintenance therapy plus isotretinoin, and continuation therapy with isotretinoin):

CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in arm II. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.

MAINTENANCE THERAPY: Patients receive maintenance therapy as in arm III. Patients then proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive continuation therapy as in arm III.

After completion of study treatment, patients are followed up periodically for up to 10 years.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Untreated Childhood Medulloblastoma
  • Untreated Childhood Pineoblastoma
  • Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor
  • 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
  • Active Comparator: Arm I (chemotherapy, RT, immunomodulating therapy)
    Patients undergo radiation therapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40 and receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 22, 29, and 36. Six weeks after completion of chemo and radiation therapy, 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 filgrastim (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.
    Interventions:
    • Drug: cyclophosphamide
    • Biological: filgrastim
    • Drug: cisplatin
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
    • Other: laboratory biomarker analysis
  • 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 sulfate as in arm I. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. Patients receive maintenance therapy as in arm I.
    Interventions:
    • Drug: carboplatin
    • Drug: cyclophosphamide
    • Biological: filgrastim
    • Drug: cisplatin
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
    • Other: laboratory biomarker analysis
  • Experimental: Arm III (chemotherapy, RT, antineoplastic therapy)
    Patients undergo chemo and radiation therapy 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 sulfate, cyclophosphamide, and filgrastim (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.
    Interventions:
    • Drug: cyclophosphamide
    • Biological: filgrastim
    • Drug: cisplatin
    • Drug: isotretinoin
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Drug: carboplatin
    • Drug: cyclophosphamide
    • Biological: filgrastim
    • Drug: cisplatin
    • Drug: isotretinoin
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Suspended
290
Not Provided
December 2012   (final data collection date for primary outcome measure)

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
Both
3 Years to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   Netherlands
 
NCT00392327
ACNS0332, NCI-2009-00336, COG-ACNS0332, CDR0000511991, ACNS0332, ACNS0332, U10CA098543, R01CA114567
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: James Olson, MD PhD Children's Oncology Group
Children's Oncology Group
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP