Clinical trial NCT00004262: Radiation Therapy and Gadolinium Texaphyrin in Treating Patients With Supratentorial Glioblastoma Multiforme
Official title: PHASE I TRIAL OF GADOLINIUM TEXAPHYRIN (PCI -0120) AS A RADIOSENSITIZER DURING STEREOTACTIC RADIOSURGERY BOOST FOR GLIOBLASTOMA MULTIFORME
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: At the time of stereotactic radiosurgery
Secondary outcomes:
measure: Concentration of gadolinium in tumor, normal brain, and plasma by plasma-atomic emission spectroscopy and liquid chromatography with mass spectrometry
timeFrame: At baseline, at 48 hours, and at 2 weeks post-surgery
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: John Grecula
role: PRINCIPAL_INVESTIGATOR
References: