Clinical Trial Finder

Inclusion Criteria:

• - Patients must have histologically proven malignant glioma (anaplastic astrocytoma, anaplastic oligodendroglioma or glioblastoma multiforme) which is progressive or recurrent after radiation therapy ± chemotherapy; patients with previous low grade glioma who progressed after radiotherapy ± chemotherapy and are biopsied and found to have a high grade glioma are eligible.

• - Patients must have measurable progressive or recurrent malignant glioma by MRI or CT imaging; (Within 14 days before starting treatment) - Patients must have recovered from toxicity of prior therapy; an interval of at least 3 months must have elapsed since the completion of the most recent course of radiation therapy, while at least 3 weeks must have elapsed since the completion of a non-nitrosourea containing chemotherapy regimen, and at least 6 weeks since the completion of a nitrosourea containing chemotherapy regimen.

• - Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others) - Absolute Neutrophil Count >= 1500/mm^3.

• - Platelets >= 100,000/mm^3.

• - Creatinine =< 1.7mg/dl.

• - Total Bilirubin =< 1.5mg/dl.

• - Transaminases =< 4 times above the upper limits of the institutional norm.

• - PT, PTT, INR within institutional norm.

• - Patients must be able to provide written informed consent.

• - Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception; women of childbearing potential must have a negative serum pregnancy test; (The anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant) - Patients must have a Mini Mental State Exam score >= 15.

Exclusion Criteria:

• - Patients with serious concurrent infection or medical illness which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety; (Examples of medical illnesses are [but not limited to] the following: uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements) - Patients who are pregnant or breast-feeding; (The anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant) - Patients who have received more than two prior treatments.

• - Patients receiving concurrent therapy for their tumor (with the exception of steroids) - Patients with a concurrent malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin; patients with a prior malignancy are ineligible unless they have been free of disease for >= five years.

• - Patients must not have any evidence of bleeding diathesis.

- Patients must not be on therapeutic anticoagulation; prophylactic anticoagulation (i.e. low dose warfarin) of venous or arterial access devices is allowed provided that the requirements for PT, INR or PTT are met; (Patients will be taken off treatment if they require therapeutic anticoagulation during BAY 43-9006 treatment)

PRIMARY OBJECTIVES:

• I. To determine the maximum tolerated dose (MTD) of BAY 43-9006 when administered to adults with recurrent malignant glioma, receiving (Group A) or not receiving (Group B) anticonvulsants known to be metabolized by the P450 hepatic enzyme complex.

• II. To assess and estimate the dose-related toxicities.

• III. To describe the pharmacokinetics of this route of administration, measuring BAY 43-9006, and to assess the pharmacokinetic difference between patients taking enzyme-inducing agents and those who are not.

• IV. To estimate overall survival.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to the concurrent use of cytochrome P450-inducing anticonvulsants (yes vs.#46;no). Patients receive oral sorafenib twice daily on days 1-28 (once daily on day 1 of course 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients per stratum receive escalating doses of sorafenib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity. Patients are followed every 2 months.

Arms

Experimental: Treatment (sorafenib tosylate)

Patients receive oral sorafenib twice daily on days 1-28 (once daily on day 1 of course 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients per stratum receive escalating doses of sorafenib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity.

Interventions

Drug: - sorafenib tosylate

Given PO

Other: - pharmacological study

Correlative studies