Radiation Therapy and Gadolinium Texaphyrin in Treating Patients With Supratentorial Glioblastoma Multiforme

Study Overview
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Brief Summary
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Phase I trial to study the effectiveness of radiation therapy and gadolinium texaphyrin in treating patients who have supratentorial glioblastoma multiforme. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as gadolinium texaphyrin may make the tumor cells more sensitive to radiation therapy.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the frequency and grade of toxicity of gadolinium texaphyrin as a radiosensitizer at two dose levels in patients with supratentorial glioblastoma multiforme undergoing stereotactic radiosurgery. II. Compare the tumor, normal brain, and plasma concentrations of this drug regimen to 1.5 and 8 Tesla MRI images in this patient population. III. Determine if the 8 Tesla images provide more data than the 1.5 Tesla images in terms of the radiosensitizing drug distribution in the tumor in these patients. OUTLINE: This is a dose escalation study. Within 5 weeks following surgery, patients receive daily external beam radiotherapy five days a week for 5 weeks. Within 2 weeks following completion of radiotherapy, patients receive gadolinium texaphyrin IV over 2 hours followed 3 hours later by stereotactic radiosurgery. Patients undergoing surgical debulking of tumor prior to external beam radiotherapy receive gadolinium texaphyrin IV over 2 hours, 3 hours prior to surgery in addition to the dose prior to stereotactic radiosurgery. Cohorts of 3-6 patients receive escalating doses of gadolinium texaphyrin until the maximum tolerated dose (MTD) is determined. 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 monthly for 3 months, and then every 3 months for 5 years or until death. PROJECTED ACCRUAL: Approximately 12-18 patients will be accrued for this study within 12-18 months.

Official Title
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PHASE I TRIAL OF GADOLINIUM TEXAPHYRIN (PCI -0120) AS A RADIOSENSITIZER DURING STEREOTACTIC RADIOSURGERY BOOST FOR GLIOBLASTOMA MULTIFORME

Conditions
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Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma

Intervention / Treatment
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* Procedure: conventional surgery
* Radiation: 3-dimensional conformal radiation therapy
* Radiation: stereotactic radiosurgery
* Drug: motexafin gadolinium
* Procedure: magnetic resonance imaging
* Procedure: spectroscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed supratentorial glioblastoma multiforme by stereotactic biopsy, open biopsy, or resection Maximum diameter of the tumor mass must be no greater than 4 cm in any dimension, including following debulking surgery Tumor must be at least 1.0 cm from the optic chiasm and brainstem No oligodendrogliomas, meningiomas, or grade I, II, or III astrocytomas No infratentorial tumors No multifocal glioblastoma multiforme Tumor enhances on MRI Must have visible tumor on postoperative MRI following surgical resection Performance status - Karnofsky 60-100% At least 3 months Hemoglobin at least 10.0 g/dL Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin no greater than 1.5 mg/dL SGPT no greater than 60 U/L Creatinine no greater than 1.3 mg/dL Blood urea nitrogen no greater than 24 mg/dL Neurological function status 0-3 No evidence of neuropathy No glucose-6-phosphate dehydrogenase deficiency No known history of porphyria History of prior malignancies allowed HIV positive status allowed No medical contraindication to MRI imaging (i.e., pacemaker, aneurysm clip, or nonsecure metal fragment close to a critical structure) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception prior to and during study At least 6 weeks since prior chemotherapy Concurrent steroids allowed No prior radiotherapy to the brain or upper neck No greater than 5 weeks since prior surgery and recovered

Ages Eligible for Study
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Minimum Age: 18 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: Treatment (motexafin gadolinium, radiotherapy, radiosurgery)<br>Within 5 weeks following surgery, patients receive daily external beam radiotherapy five days a week for 5 weeks. Within 2 weeks following completion of radiotherapy, patients receive gadolinium texaphyrin IV over 2 hours followed 3 hours later by stereotactic radiosurgery. Patients undergoing surgical debulking of tumor prior to external beam radiotherapy receive gadolinium texaphyrin IV over 2 hours, 3 hours prior to surgery in addition to the dose prior to stereotactic radiosurgery. | Procedure: conventional surgery<br> <br> * Other names: surgery, conventional;Radiation: 3-dimensional conformal radiation therapy<br> <br> * Other names: 3D-CRT;Radiation: stereotactic radiosurgery<br> <br> Drug: motexafin gadolinium<br>* Given IV<br>* Other names: Xcytrin;Procedure: magnetic resonance imaging<br>* Undergo MRI with both the clinical 1.5 Tesla and research 8 Tesla magnets<br>* Other names: nuclear magnetic resonance imaging;Procedure: spectroscopy<br>* Undergo plasma-atomic emission spectroscopy (DCP-AES)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT), as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 2.0 |  | At the time of stereotactic radiosurgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of gadolinium in tumor, normal brain, and plasma by plasma-atomic emission spectroscopy and liquid chromatography with mass spectrometry |  | At baseline, at 48 hours, and at 2 weeks post-surgery |