motexafin gadolinium in treating patients with glioblastoma multiforme who are undergoing radiation therapy to the brain

Conditions: Brain and Central Nervous System Tumors

Summary: 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.

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.

Eligibility criteria:
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

Keywords: adult glioblastoma adult giant cell glioblastoma adult gliosarcoma