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

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00032097
• Other study ID #: CDR0000069257
• Secondary ID: NABTT-2116JHOC-N
• Status: Completed
• Phase: Phase 1
• First received: March 8, 2002
• Last updated: February 6, 2009
• Start date: April 2002

Study information

• Verified date: January 2004
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioblastoma
• Nervous System Neoplasms

Intervention

Drug:
• motexafin gadolinium

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,