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

PHASE I TRIAL OF GADOLINIUM TEXAPHYRIN (PCI -0120) AS A RADIOSENSITIZER DURING STEREOTACTIC RADIOSURGERY BOOST FOR GLIOBLASTOMA MULTIFORME

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.

Study Overview

• Status: Completed
• Conditions: Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma
• Intervention / Treatment: Procedure: conventional surgery; Radiation: stereotactic radiosurgery; Drug: motexafin gadolinium; Radiation: 3-dimensional conformal radiation therapy; Procedure: magnetic resonance imaging; Procedure: spectroscopy

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.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (motexafin gadolinium, radiotherapy, radiosurgery); 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.

Procedure: conventional surgery; Other Names: surgery, conventional; Radiation: stereotactic radiosurgery; Drug: motexafin gadolinium; Given IV; Other Names: gadolinium texaphyrin; Gd (III) Texaphryin; Gd-Tex; PCI-0120; Xcytrin; Radiation: 3-dimensional conformal radiation therapy; Other Names: 3D-CRT; 3D conformal radiation therapy; Procedure: magnetic resonance imaging; Undergo MRI with both the clinical 1.5 Tesla and research 8 Tesla magnets; Other Names: MRI; NMRI; nuclear magnetic resonance imaging; NMR imaging; Procedure: spectroscopy; Undergo plasma-atomic emission spectroscopy (DCP-AES)

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: John Grecula, Ohio State University

Study record dates

Study Major Dates

• Study Start: November 1, 1999
• Primary Completion (Actual): May 1, 2005

Study Registration Dates

• First Submitted: January 28, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): June 4, 2013
• Last Update Submitted That Met QC Criteria: June 3, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Gliosarcoma; Antineoplastic Agents; Photosensitizing Agents; Dermatologic Agents; Motexafin gadolinium
• Other Study ID Numbers: NCI-2012-01400; U01CA076576 (U.S. NIH Grant/Contract); 99H0239; CDR0000067517; NCI-T99-0041; OSU-9976; OSU-99H0239