Trial record 1 of 1 for:    COG ACNS0332
Previous Study | Return to List | Next Study

Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Previously Untreated, High-Risk Medulloblastoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00392327
First received: October 25, 2006
Last updated: September 3, 2014
Last verified: September 2014

October 25, 2006
September 3, 2014
March 2007
November 2015   (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 10 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.
Not Provided
Complete list of historical versions of study NCT00392327 on ClinicalTrials.gov Archive Site
  • Tumor response to radiation therapy with or without carboplatin [ Time Frame: Up to 10 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-radiation therapy response rate between the two treatment groups.
  • Time to death [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Survival 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
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 studies different chemotherapy and radiation therapy regimens to compare how well they work in treating young patients with newly diagnosed, previously untreated, high-risk medulloblastoma. Drugs used in chemotherapy, such as vincristine sulfate, cisplatin, cyclophosphamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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. To determine whether carboplatin radiosensitization increases long term event-free survival for high risk medulloblastoma/primitive neuroectodermal tumor (PNET) patients.

II. To determine whether isotretinoin increases long term event-free survival for high risk medulloblastoma/PNET patients.

SECONDARY OBJECTIVES:

I. To compare residual disease response to radiation alone versus radiation plus carboplatin.

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

III. To evaluate the health-related quality of life (HRQOL) during phases of active treatment specific to treatment modalities.

IV. To describe the neuropsychological functioning of the study population and to evaluate the relationship between neuropsychological status and health related quality of life.

OUTLINE: Patients are randomized to 1 of 4 treatment arms.

ARM I (standard chemoradiotherapy and standard maintenance therapy):

CHEMORADIOTHERAPY: Patients undergo radiation therapy once daily (QD) five days a week for 6 weeks. Patients also receive vincristine sulfate intravenously (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 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 vincristine sulfate and undergo radiation therapy as in Arm I. 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 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 isotretinoin orally (PO) twice daily (BID) on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim 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 isotretinoin PO BID on days 15-28 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
  • Radiation: radiation therapy
    Undergo radiation therapy
    Other Names:
    • irradiation
    • radiotherapy
    • therapy, radiation
  • Drug: vincristine sulfate
    Given IV
    Other Names:
    • leurocristine sulfate
    • VCR
    • Vincasar PFS
  • Drug: carboplatin
    Given IV
    Other Names:
    • Carboplat
    • CBDCA
    • JM-8
    • Paraplat
    • Paraplatin
  • Drug: cisplatin
    Given IV
    Other Names:
    • CACP
    • CDDP
    • CPDD
    • DDP
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Biological: filgrastim
    Given IV or SC
    Other Names:
    • G-CSF
    • Neupogen
  • Drug: isotretinoin
    Given PO
    Other Names:
    • 13-CRA
    • Amnesteem
    • Cistane
    • Claravis
    • Sotret
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: quality-of-life assessment
    Ancillary studies
    Other Name: quality of life assessment
  • Active Comparator: Arm I (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.

    Interventions:
    • Radiation: radiation therapy
    • Drug: vincristine sulfate
    • Drug: cisplatin
    • Drug: cyclophosphamide
    • Biological: filgrastim
    • Other: laboratory biomarker analysis
    • Other: quality-of-life assessment
  • Experimental: Arm II (chemoradiotherapy)

    CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm I. 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 I.

    Interventions:
    • Radiation: radiation therapy
    • Drug: vincristine sulfate
    • Drug: carboplatin
    • Drug: cisplatin
    • Drug: cyclophosphamide
    • Biological: filgrastim
    • Other: laboratory biomarker analysis
    • Other: quality-of-life assessment
  • Experimental: Arm III (chemoradiotherapy, isotretinoin)

    CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm I. 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 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 isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

    Interventions:
    • Radiation: radiation therapy
    • Drug: vincristine sulfate
    • Drug: cisplatin
    • Drug: cyclophosphamide
    • Biological: filgrastim
    • Drug: isotretinoin
    • Other: laboratory biomarker analysis
    • Other: quality-of-life assessment
  • Experimental: Arm IV (chemoradiotherapy, 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.

    Interventions:
    • Radiation: radiation therapy
    • Drug: vincristine sulfate
    • Drug: carboplatin
    • Drug: cisplatin
    • Drug: cyclophosphamide
    • Biological: filgrastim
    • Drug: isotretinoin
    • Other: laboratory biomarker analysis
    • Other: quality-of-life assessment
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
400
Not Provided
November 2015   (final data collection date for primary outcome measure)

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
  • Patients taking Accutane (isotretinoin) for acne must discontinue drug use with this indication prior to enrollment; corticosteroids should not be used during chemotherapy administration as an antiemetic

    • Isotretinoin is contraindicated in patients with parabens allergy and patients with soybean allergy; concurrent use with tetracyclines should be avoided; intake of vitamin A should be limited for the duration of isotretinoin treatment
  • 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:

    • 0.4 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)
  • 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
Both
3 Years to 21 Years
No
United States,   Australia,   Canada,   Netherlands,   Puerto Rico
 
NCT00392327
ACNS0332, NCI-2009-00336, COG-ACNS0332, CDR0000511991, ACNS0332, ACNS0332, R01CA114567, U10CA098543, U10CA180886
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
September 2014

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