Cooperative Multicenter Study for Children and Adolescents With Low Grade Glioma
- 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,
- 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
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
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
week 24, and at 1, 3, and 5 years
Germany: Federal Institute for Drugs and Medical Devices