Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma
Conditions
Brief summary
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
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.
Interventions
PROCEDUREconventional surgery
RADIATION3-dimensional conformal radiation therapy
RADIATIONstereotactic radiosurgery
DRUGmotexafin gadolinium
Given IV
PROCEDUREmagnetic resonance imaging
Undergo MRI with both the clinical 1.5 Tesla and research 8 Tesla magnets
PROCEDUREspectroscopy
Undergo plasma-atomic emission spectroscopy (DCP-AES)
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
United States
Outcome results
None listed