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

Phase 1
Completed
Conditions
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Interventions
Procedure: conventional surgery
Radiation: 3-dimensional conformal radiation therapy
Radiation: stereotactic radiosurgery
Procedure: magnetic resonance imaging
Procedure: spectroscopy
Registration Number
NCT00004262
Lead Sponsor
National Cancer Institute (NCI)
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
12
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
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (motexafin gadolinium, radiotherapy, radiosurgery)conventional surgeryWithin 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.
Treatment (motexafin gadolinium, radiotherapy, radiosurgery)3-dimensional conformal radiation therapyWithin 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.
Treatment (motexafin gadolinium, radiotherapy, radiosurgery)stereotactic radiosurgeryWithin 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.
Treatment (motexafin gadolinium, radiotherapy, radiosurgery)magnetic resonance imagingWithin 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.
Treatment (motexafin gadolinium, radiotherapy, radiosurgery)spectroscopyWithin 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.
Treatment (motexafin gadolinium, radiotherapy, radiosurgery)motexafin gadoliniumWithin 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.
Primary Outcome Measures
NameTimeMethod
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 2.0At the time of stereotactic radiosurgery
Secondary Outcome Measures
NameTimeMethod
Concentration of gadolinium in tumor, normal brain, and plasma by plasma-atomic emission spectroscopy and liquid chromatography with mass spectrometryAt baseline, at 48 hours, and at 2 weeks post-surgery

Trial Locations

Locations (1)

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

🇺🇸

Columbus, Ohio, United States

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