Temozolomide and Radiation Therapy in Treating Young Patients With Pontine Glioma

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving temozolomide together with radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving temozolomide together with radiation therapy works in treating young patients with pontine glioma.

Detailed Description
-----------------
OBJECTIVES: Primary To evaluate the time to death in patients with newly diagnosed diffuse pontine gliomas, when treated with the combination of concomitant low-dose oral temozolomide and radiotherapy, followed by up to 12 months of maintenance therapy with extended low-dose temozolomide. To assess the quality of life of patients with diffuse pontine gliomas during and after treatment. Secondary To evaluate the time to tumor progression in patients with newly diagnosed diffuse pontine gliomas, when treated with the combination of concomitant low-dose oral temozolomide and radiotherapy, followed by up to 12 months of maintenance therapy with extended low-dose temozolomide. To evaluate and document toxicities from the administration of temozolomide combined with radiotherapy and to further study any toxicities associated with the chronic administration of the extended low-dose temozolomide schedule in this population group. To document radiological response to the above treatment with MR imaging and, where available, functional imaging. OUTLINE: This is a multicenter study. Chemoradiotherapy: Patients receive oral temozolomide once daily for 6 weeks (7 days per week) with concurrent radiotherapy (5 days per week). Patients without evidence of disease progression proceed to maintenance therapy beginning at least 4 weeks after completion of radiotherapy. Maintenance therapy: Patients receive oral temozolomide daily on days 1-21. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Quality of life is assessed prior to chemoradiotherapy and prior to course 1 of adjuvant temozolomide and prior to every 3 subsequent courses of adjuvant temozolomide. After completion of study therapy, patients are followed every 8 weeks.

Official Title
-----------------
A Phase II Multi-Centre Study of Concomitant and Prolonged Adjuvant Temozolomide With Radiotherapy in Diffuse Pontine Gliomas

Conditions
-----------------
Brain and Central Nervous System Tumors

Intervention / Treatment
-----------------
* Drug: motexafin gadolinium
* Drug: temozolomide
* Procedure: adjuvant therapy
* Procedure: quality-of-life assessment
* Radiation: radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Inclusion criteria: Newly diagnosed diffuse intrinsic lesion centered in the pons on MRI No requirement for histological diagnosis Clinical history < 6 months Clinical findings must include at least 1 of the 3 following signs of brainstem tumor: Cranial nerve deficit Long tract signs Ataxia Exclusion criteria: Focal lesions of brainstem Predominantly exophytic tumors PATIENT CHARACTERISTICS: Inclusion criteria: Karnofsky performance status (PS) or Lansky PS 60-100% (unless reason for decrease in status is a direct result of neurological involvement of the brainstem glioma) Life expectancy > 12 weeks Absolute neutrophil count ≥ 1,000/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 10 g/dL Urea and serum creatinine < 1.5 times upper limit of normal (ULN) Total and direct bilirubin < 1.5 times ULN AST and ALT < 3 times ULN Negative pregnancy test within 7 days prior to administration of temozolomide for women of childbearing potential Exclusion criteria: Frequent vomiting and/or medical condition, that could interfere with oral medication intake (e.g., partial bowel obstruction) Pregnant or breast-feeding women PRIOR CONCURRENT THERAPY: Exclusion criteria: Prior chemotherapy or radiotherapy Other concurrent investigational drugs Other concurrent chemotherapy, immunotherapy, or biologic therapy

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: motexafin gadolinium|nan|
|Drug: temozolomide|nan|
|Procedure: adjuvant therapy|nan|
|Procedure: quality-of-life assessment|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  |  | 
| Quality of life including health status, behavior, and the subjective experience using HUI and SDQ methods |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity, steroid usage, and radiological response |  |  | 
| Adverse events, including abnormal laboratory parameters, as assessed by CTC criteria |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
untreated childhood brain stem glioma