Motexafin Gadolinium in Treating Patients With Glioblastoma Multiforme Who Are Undergoing Radiation Therapy to the Brain

NCT ID: NCT00032097

Last Updated: 2009-02-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-04-30

Brief 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.

Detailed Description

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Primary Study Purpose: TREATMENT

Interventions

motexafin gadolinium

Intervention Type: DRUG

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Principal Investigators

James L. Pearlman, MD

Role: STUDY_CHAIR

H. Lee Moffitt Cancer Center and Research Institute

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

NABTT-2116

Identifier Type: -

Identifier Source: secondary_id

JHOC-NABTT-2116

Identifier Type: -

Identifier Source: secondary_id

CDR0000069257

Identifier Type: -

Identifier Source: org_study_id