Motexafin Gadolinium in Treating Patients With Glioblastoma Multiforme Who Are Undergoing Radiation Therapy to the Brain

Study Overview
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Brief Summary
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RATIONALE: 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. PURPOSE: Phase I trial to study the effectiveness motexafin gadolinium in treating patients with glioblastoma multiforme who are undergoing radiation therapy to the brain.

Detailed Description
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OBJECTIVES: Determine the toxicity of 2 different schedules of motexafin gadolinium as a radiosensitizer in patients with glioblastoma multiforme receiving cranial radiotherapy. Determine the maximum tolerated doses of this drug on these 2 schedules in these patients. Determine the pharmacokinetic profile of this drug in these patients. Determine the biodistribution of this drug in both neoplastic tissue and normal brain parenchyma in these patients. Determine the effect and accumulation of this drug in both normal brain parenchyma and neoplastic tissue in these patients. Correlate the effect and accumulation of this drug in both normal brain parenchyma and neoplastic tissue with the pharmacokinetics of this drug in these patients. OUTLINE: This is a multicenter, dose-escalation study of motexafin gadolinium (PCI-0120). Patients are sequentially assigned to 1 of 2 treatment groups. Group I: Patients receive PCI-0120 IV over 30-60 minutes once every other day for 6 weeks. Patients concurrently undergo cranial radiotherapy once daily 5 days a week for 6 weeks. Group II: Patients receive PCI-0120 IV over 30-60 minutes once daily concurrently during radiotherapy. Patients undergo cranial radiotherapy as in group I. Cohorts of 3-6 patients in each group receive escalating doses of PCI-0120 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Patients are followed at 1 month and then every 2 months thereafter. PROJECTED ACCRUAL: Approximately 18-30 patients will be accrued for this study.

Official Title
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A Phase I Trial To Evaluate Repetitive Intravenous Doses Of Gadolinium-Texaphyrin As A Radiosensitizer In Patients With Glioblastoma Multi Forme

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: motexafin gadolinium
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed supratentorial grade IV astrocytoma Glioblastoma multiforme Previously untreated disease Measurable and contrast-enhancing tumor by MRI after incomplete resection/biopsy PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: WBC at least 3,000/mm^3 Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10 g/dL Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT/SGPT no greater than 4 times upper limit of normal (ULN) Alkaline phosphatase no greater than 4 times ULN PT/APTT normal Renal: Creatinine no greater than 1.5 mg/dL Cardiovascular: No uncontrolled hypertension Other: Mini mental state exam score at least 15 No history of glucose-6-phosphate dehydrogenase deficiency or porphyria No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or carcinoma in situ of the breast No serious infection No other medical illness that would preclude study participation No allergy to MRI contrast (e.g., motexafin gadolinium) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for up to 2 months after study PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy or immunotherapy for this disease, including any of the following: Immunotoxins Immunoconjugates Antisense therapy Peptide receptor antagonists Interferons Interleukins Tumor-infiltrating lymphocytes Lymphokine-activated killer cell therapy Gene therapy Chemotherapy: No prior chemotherapy for this disease Endocrine therapy: Must be on a stable corticosteroid regimen (i.e., no increase within 5 days prior to treatment on this protocol) No other prior hormonal therapy for this disease Radiotherapy: No prior radiotherapy for this disease Surgery: See Disease Characteristics Recovered from prior surgery Other: No other concurrent investigational agents

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: motexafin gadolinium|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma