Sorafenib in Treating Patients With Recurrent or Progressive Malignant Glioma
Sorafenib in Treating Patients With Recurrent or Progressive Malignant Glioma
This phase I trial is studying the side effects and best dose of sorafenib in treating
 patients with recurrent or progressive malignant glioma. Sorafenib may stop the growth of
 tumor cells by stopping blood flow to the tumor and by blocking the enzymes necessary for
 their growth.
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 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.
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)