Radiation Therapy or Combination Chemotherapy in Treating Patients With Clinically or Radiologically Progressive Low-Grade Gliomas
Condition: Primary Central Nervous System Neoplasms
MeSH terms: Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional

Summary: 
      RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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.

      PURPOSE: This clinical trial is studying giving radiation therapy or combination chemotherapy
      to see how well it works in treating patients with clinically or radiologically progressive
      low-grade gliomas.
    

Detailed description: 
      OBJECTIVES:

        -  Provide a comprehensive treatment strategy for children and adolescents with low-grade
           glioma of all tumour locations and histologies.

        -  Provide standardized treatment indication and treatment recommendations for non-surgical
           therapy in children and adolescents with low grade glioma without and with associated
           neurofibrosis-type 1 (NF1) at diagnosis or after observation.

        -  Determine overall, event-free, and progression-free survival.

        -  Radiotherapy arm: a. Determine progression free survival in older children without NF1
           treated with radiotherapy using modern techniques for planning and treatment. b.
           Determine the reduction of the rate and intensity of possible late effects of therapy to
           the organs at risk by optimized planning and treatment.

        -  Chemotherapy arm: a. Determine progression free survival for younger children without
           NF1 treated with chemotherapy and randomized to either the 2-drug or the 3-drug
           induction regimen. b. Determine the distribution of response at week 24 (after
           induction) for younger children without NF1 treated with chemotherapy and randomized to
           either the 2-drug or the 3-drug induction regimen. c. Determine progression free
           survival for children with NF1treated with chemotherapy.

        -  Determine the influence of clinical and histological findings on overall survival,
           progression-free and event-free survival in these patients.

        -  Determine prospectively the late effects of tumor and therapy in these patients.

      OUTLINE: This is a partially randomized, open-label, multicenter study.

      Children with completely resected tumors, incompletely resected tumors, or those with
      clinically/neuroradiologically diagnosed tumors, who do not have severe symptoms at
      diagnosis, are only observed during follow-up.

      Children with unresectable/incompletely-resectable tumors, or those with relapsed disease and
      those observed following incomplete initial resection or neuroradiologic diagnosis and
      clinical and/or neuro-radiologic progression receive non-surgical therapy. This non-surgical
      therapy is either chemotherapy (for children younger than 8 years and those with
      neurofibrosis-type 1 [NF1]) or radiotherapy (for children older than 8 years).

        -  Chemotherapy: Within the chemotherapy arm, patients without NF1 are randomized to
           receive 1 of 2 induction chemotherapy regimens. Patients with NF1 receive the two-drug
           induction therapy as in arm I.

             -  Arm I (two-drug induction therapy [vincristine-carboplatin] ): Patients receive
                induction therapy comprising vincristine IV on day 1 of weeks 1-10 and weeks 13,
                17, and 21 and carboplatin IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 17,
                and 21.

             -  Arm II (three-drug induction therapy [vincristine-carboplatin-etoposide]): Patients
                receive vincristine and carboplatin as in two-drug induction therapy. Patients also
                receive etoposide IV over 1 hour on days 1-3 of weeks 1, 4, 7, and 10.

      Beginning in week 25, all patients in the chemotherapy arm receive consolidation therapy
      comprising vincristine IV on days 1, 8, and 15 and carboplatin IV over 1 hour on day 1.
      Treatment repeats every 6 weeks for 9 courses. Patients experiencing disease progression or
      an allergic reaction to carboplatin receive vincristine IV on days 1, 8, and 15 and either
      cyclophosphamide IV over 1 hour on day 1 or cisplatin IV over 3 hours on days 1 and 2.
      Treatment repeats every 6 weeks for 5 courses. All patients in the chemotherapy arm receive a
      total of 18 months of treatment.

        -  Radiotherapy: Conventional external beam fractionated radiotherapy is given at standard
           doses for children receiving radiotherapy. Brachytherapy can be given, if tumors are
           suitable for this type of treatment.

      After completion of study treatment, patients are followed periodically for 10 years.

      PROJECTED ACCRUAL: A total of 520 patients will be accrued for the randomized arm of this
      study.
    

Intervention name(s): vincristine, carboplatin; vincristine, carboplatin, etoposide; radiation therapy
Intervention type(s): Drug; Drug; Radiation
Intervention description(s): vincristine: 1,5 mg/m² i.v., week 1,2,3,4,5,6,7,8,9,10,13,17,21
carboplatin: 550 mg/m² i.v., week 1,4,7,10,13,17,21; vincristine: 1,5 mg/m² i.v., week 1,2,3,4,5,6,7,8,9,10,13,17,21
carboplatin: 550 mg/m² i.v., week 1,4,7,10,13,17,21
etoposide: 100 mg/m² i.v., week 1,4,7,10; intracranial tumor site: 30 fractions, dose per fraction: 1.8 Gy, total dose: 54 Gy, duration 6 weeks
spinal tumor site: 28 fractions, dose per fraction: 1.8 Gy, total dose: 50.4 Gy duration 5 1/2 weeks
Intervention MeSH terms: Carboplatin; Etoposide; Vincristine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent childhood brain stem glioma; untreated childhood brain stem glioma; recurrent childhood cerebellar astrocytoma; untreated childhood cerebellar astrocytoma; childhood low-grade cerebral astrocytoma; recurrent childhood cerebral astrocytoma; childhood oligodendroglioma; recurrent childhood visual pathway and hypothalamic glioma; untreated childhood visual pathway and hypothalamic glioma; childhood spinal cord neoplasm