Motexafin Gadolinium and Radiation Therapy in Treating Young Patients With Pontine Glioma

PRIMARY OBJECTIVES:

I. Evaluate the effect of combining motexafin gadolinium with daily fractionated radiotherapy on 1-year event-free survival of pediatric patients with intrinsic pontine glioma (brain stem glioma).

SECONDARY OBJECTIVES:

I. Evaluate the effect of combining motexafin gadolinium with daily fractionated radiotherapy on 1-year overall survival of these patients.

II. Determine the toxicities of motexafin gadolinium in combination with radiotherapy in these patients.

OUTLINE: This is a multicenter study.

Patients receive motexafin gadolinium IV over 5-10 minutes once daily (prior to radiotherapy) 5 days a week for 6 weeks. Patients undergo focal cranial radiotherapy once daily 5 days a week for 6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 3 years and then periodically thereafter.

Inclusion criteria

• Diagnosis of intrinsic pontine glioma (brain stem glioma)

• Clinical and radiographic (MRI) evidence of tumors that diffusely involve the brain stem (i.e., tumors that intrinsically [> 50% intra-axial] involve the pons or pons and medulla, pons and midbrain, or entire brain stem) allowed
• Tumor may contiguously involve the thalamus or upper cervical cord
• No more than 1 lesion/mass present at diagnosis
• Karnofsky performance status (PS) 60-100% (age > 16 years) OR Lansky PS 60-100% (age ≤ 16 years)
• Life expectancy ≥ 8 weeks
• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 100,000/mm³ (transfusion independent)
• Hemoglobin ≥ 10 g/dL (RBC transfusions allowed)
• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine normal for age/gender (0.4-1.7 mg/dL)
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT < 1.5 times ULN
• No known glucose-6-phosphate dehydrogenase (G6PD) deficiency

• If family history suggestive of congenital hemolytic anemia, patient must be screened for G6PD with G6PD activity test prior to study entry
• No biliary obstruction
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior definitive therapy for this specific tumor
• No prior cranial radiotherapy
• Concurrent steroids and anticonvulsants allowed
• No concurrent proton therapy
• No concurrent intensity-modulated radiotherapy
• No concurrent anticancer chemotherapy
• No concurrent immunomodulating agents