A study for all children and adolescents with a low grade glioma.

The study SIOP-LGG 2004 offers a common therapy strategy for all children and adolescents with a histologically ( WHO criteria ) or radiologically confirmed low grade glioma. Following complete resection patients will only be observed, as will be patients without symptoms or progression after incomplete resection or clinical diagnosis. Non-surgical therapy will be instituted at the presence of defined indications following incomplete resection, non-resectable relapse or progression of an unresectable tumor.
Older children (³ 8 years) receive primary radiotherapy. Modern planning and treatment techniques shall reduce long term side effects upon surrounding tissues and organs at risk. At the presence of specific conditions these children may receive chemotherapy as well. The indication for interstitial radiotherapy is not age restricted. Younger children (< 8 years) receive primary chemotherapy. Children affected by Neurofibromatosis NF I shall be treated with chemotherapy at all ages. The duration of chemotherapy is 18 months. Children without NF I (stratified for age and tumor localization) will be randomized to receive standard induction with Vincristin and Carboplatin or intensified induction with Vincristin, Carboplatin and Etoposide, to test, if there is a difference in progression free survival. Additionally the distribution of tumor response at week 24 shall be investigated. Consolidation consists of ten 6-week cycles of Vincristin/Carboplatin therapy. For all children overall survival, progression free and event free survival will be calculated. The influence of clinical and histologic findings upon these parameters will be investigated. The extent of late effects of primary tumor and therapy shall be documented prospectively.

The goal of this study is:

1. To offer a uniform, standardized concept for the treatment of children and adolescents affected by low grade glioma;

2. To improve progression free survival following non-surgical therapy for children without NFI with low grade glioma (incl. randomisation standard vs intensified induction therapy);

3. To investigate standardized treatment recommendations for non-surgical therapy for the study group of children with NFI and low grade glioma;

4. To reduce the rate and intensity of possible late effects of therapy.

1. PFSr: Progression free survival measured from the time of randomization: Time
from randomization up to an event:
Definition of event:

A. Death (for all reasons);

B. Progression of a residual tumor;

C. Relapse following previous complete remission;

D. Appearance of new or progression of existing metastasis.

2. Radiological response measured at week 24: Complete, partial, objective responses
and stable disease will be considered positive responses in this protocol;

3. PFSd: Progression free survival measured from the time of diagnosis: Time from diagnosis up to an event (definitions of event see 1.);

4. EFSr: Event free survival measured from the time of randomization: Time from
randomization up to an event.
Definition of event:

A. Death (for all reasons);

B. Progression of a residual tumor;

C. Relapse following previous complete remission;

D. Appearance of new or progression of existing metastasis;

E. Severe adverse event / toxicity (not counting Carboplatin hypersensitivity and toxicity of regular protocol application);

F. Appearance of secondary malignant neoplasm.

5. EFSd: Event free survival measured from the time of diagnosis: Time from
diagnosis up to an event. (definition of event: see 4.);

6. OSr: Overall survival measured from the time of randomization: Interval starting
with the day of randomization and ending with the death of the patient
independently of its cause;

7. OSd: Overall survival measured from the time of diagnosis: Interval starting with
the day of diagnosis and ending with the death of the patient independently of its
cause.

Following complete resection patients will only be observed, as will be patients without symptoms or progression after incomplete resection or clinical diagnosis. Non-surgical therapy will be instituted at the presence of defined indications following incomplete resection, non-resectable relapse or progression of an unresectable tumor.

Older children (>= 8 years) receive primary radiotherapy. Modern planning and treatment techniques shall reduce long term side effects upon surrounding tissues and organs at risk. At the presence of specific conditions these children may receive chemotherapy as well. The indication for interstitial radiotherapy is not age restricted. Younger children (< 8 years) receive primary chemotherapy. Children affected by Neurofibromatosis NF I shall be treated with chemotherapy at all ages. The duration of chemotherapy is 18 months. Children without NF I (stratified for age and tumor localization) will be randomized to receive standard induction with Vincristin and Carboplatin or intensified induction with Vincristin, Carboplatin and Etoposide, to test, if there is a difference in progression free survival. Additionally the distribution of tumor response at week 24 shall be investigated. Consolidation consists of ten 6-week cycles of Vincristin/Carboplatin therapy.