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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00032097

Collaborator

(none)

Location

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: motexafin gadolinium Radiation: radiation therapy	Phase 1

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Phase I Trial To Evaluate Repetitive Intravenous Doses Of Gadolinium-Texaphyrin As A Radiosensitizer In Patients With Glioblastoma Multi Forme

Study Start Date :

Apr 1, 2002

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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