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

Study Overview
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Brief Summary
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This phase II trial is studying how well giving motexafin gadolinium together with radiation therapy works in treating young patients with pontine glioma. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as motexafin gadolinium, may make tumor cells more sensitive to radiation therapy. Giving motexafin gadolinium together with radiation therapy may kill more tumor cells.

Detailed Description
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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.

Official Title
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A Phase II Study of Motexafin-Gadolinium (NSC 695238, IND #55583) and Involved Field Radiation Therapy for Intrinsic Pontine Glioma of Childhood

Conditions
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Untreated Childhood Brain Stem Glioma

Intervention / Treatment
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* Drug: motexafin gadolinium
* Radiation: 3-dimensional conformal radiation therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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. | Drug: motexafin gadolinium<br>* Given IV<br>* Other names: Xcytrin;Radiation: 3-dimensional conformal radiation therapy<br>* Undergo focal cranial radiotherapy<br>* Other names: 3D-CRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One Year Event-free Survival (EFS) | Percentage probability of being event-free at 1 year following enrollment. | One year after enrollment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Percentage probability of being alive 1 year following enrollment. | One year after enrollment. | 
| The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity. | Occurrence of serious toxicity defined as any grade 4 hematologic toxicity that persists for more than 7 days or requires platelet transfusions for a time period exceeding 7 days; any grade 3 or 4 non-hematologic toxicity with the exception of grade 3 nausea or vomiting which can be controlled within 7 days; grade 3 skin reaction; grade 3 transaminitis. | One cycle of chemotherapy and radiation therapy; expected to be 42 days of treatment. |