Phase I – Objectives

Primary Objective
To determine the maximum tolerated dose (MTD) of Tetra-O-Methyl Nordihydroguaiaretic Acid (EM-1421) administered as a daily intravenous infusion for 5 consecutive days every 28 days to adults with recurrent high grade glioma, receiving anticonvulsants that induce hepatic metabolic enzymes (Group A) or not receiving anticonvulsants or receiving anticonvulsants with modest induction or no induction of hepatic metabolic enzymes (Group B).

Secondary Objectives

1. To describe the pharmacokinetics of this route of administration, measuring EM-1421, and to determine the effects of hepatic enzyme-inducing drugs, anticonvulsants, on the pharmacokinetics.
   
2. To estimate the toxicity and to assess the tolerability associated with EM-1421.
   
3. To assess the anti-tumor activity in terms of overall survival.

Phase II – Objectives

Primary Objective To estimate the response rates of adult patients with recurrent high grade glioma treated with EM-1421 administered at the MTD.

Secondary Objectives

1. To assess overall survival.
   
2. To assess the safety and tolerability associated with the EM-1421 given at the MTD in patients with recurrent high grade glioma.

Brief Eligibility Criteria

1. Patients must be at least 18 years of age.
   
2. Patients must have histologically proven malignant glioma (anaplastic astrocytoma, anaplastic oliogodendroglioma 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.
   
3. Patients must have contrast enhancing measurable progressive or recurrent malignant glioma by MRI or CT imaging. (Within 14 days before starting treatment).