Motexafin Gadolinium Plus Radiation Therapy in Treating Children With Newly Diagnosed Brain Stem Glioma

Study Overview
=================
Brief Summary
-----------------
Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as motexafin gadolinium may make the tumor cells more sensitive to radiation therapy. Phase I trial to study the effectiveness of motexafin gadolinium plus radiation therapy in treating children who have newly diagnosed brain stem glioma

Detailed Description
-----------------
OBJECTIVES: I. Determine the maximum tolerated dose (MTD) and schedule of motexafin gadolinium administered prior to radiotherapy in children with newly diagnosed diffuse intrinsic pontine glioma. II. Determine the toxic effects of this drug given at the MTD in these patients. III. Determine the intratumor and brain distribution of this drug by magnetic resonance imaging (MRI) in these patients. OUTLINE: This is a dose-escalation study of motexafin gadolinium. Approximately 2-5 hours before radiotherapy, patients receive motexafin gadolinium IV over 5 minutes. Patients undergo radiotherapy 5 days a week for 6 weeks. Cohorts of 3-6 patients receive escalating doses of motexafin gadolinium until the MTD is determined. The first cohort receives motexafin gadolinium 5 days a week for 3 weeks; the second cohort receives motexafin gadolinium 3 days a week for 6 weeks; and subsequent cohorts receive motexafin gadolinium 5 days a week for 6 weeks. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 3 months for up to 3 years. PROJECTED ACCRUAL: A maximum of 24 patients will be accrued for this study within 2 years.

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

Conditions
-----------------
Untreated Childhood Brain Stem Glioma

Intervention / Treatment
-----------------
* Drug: motexafin gadolinium
* Radiation: radiation therapy
* Other: pharmacological study


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinically and radiographically (MRI) proven newly diagnosed diffuse intrinsic brainstem glioma Greater than 50% intra-axial involvement of the pons, pons and medulla, pons and midbrain, or entire brainstem Contiguous involvement of the thalamus or upper cervical cord allowed Performance status - ECOG 0-2 More than 2 months Absolute neutrophil count at least 1,000/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10.0 g/dL (transfusion allowed) No glucose 6 phosphate dehydrogenase deficiency Bilirubin no greater than 1.5 times normal SGOT or SGPT less than 1.5 times normal Creatinine no greater than 1.5 times normal Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No concurrent immunomodulating agents No other concurrent chemotherapy Concurrent corticosteroid therapy allowed for increased intracranial pressure only No prior cranial radiotherapy No prior motexafin gadolinium No other concurrent experimental agents

Ages Eligible for Study
-----------------
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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Approximately 2-5 hours before radiotherapy, patients receive motexafin gadolinium IV over 5 minutes. Patients undergo radiotherapy 5 days a week for 6 weeks. | Drug: motexafin gadolinium<br>* Given IV<br>* Other names: Xcytrin;Radiation: radiation therapy<br>* Undergo radiation therapy<br>* Other names: therapy, radiation;Other: pharmacological study<br>* Correlatives studies<br>* Other names: pharmacological studies;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD defined as the dose at which fewer than one-third of patients experience DLT assessed using CTC version 2.0 |  | 6 weeks |