Overview

This is a phase II open-label study investigating the efficacy, safety and pharmacokinetic(PK) properties of OKN-007 combined with temozolomide(TMZ) in patients with recurrent glioblastoma(GBM). All patients will have been previously treated with the standard-of-care treatment which includes surgical resection, radiation and chemotherapy, and in some cases treatment for recurrent disease. Patients with unequivocal recurrence (first or greater) established by MRI and meeting inclusion and exclusion criteria, will be eligible for OKN-007 treatment on this protocol.

Eligibility

Inclusion Criteria:

1. Confirmed histopathology of recurrent GBM (WHO Grade IV), following primary treatment with TMZ and radiotherapy (minimum of 50 Gy) and at least two cycles of maintenance TMZ (5 days of a 28 day cycle).
2. Patients must have tumor tissue samples available from the GBM surgery or open biopsy for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status analysis or must have medical record available to document MGMT status.
3. Unequivocal radiographic evidence of tumor progression by MRI
4. At least one measurable lesion per RANO criteria within 21 days prior to registration.
5. No more than one prior line of therapy for glioblastoma.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
7. Full recovery ( grade 1) from the toxic effects.
8. Adequate renal, liver and bone marrow function:
   • Hemoglobin >9.0 g/dL
   • Leukocytes >3,000/mcL
   • Absolute neutrophil count >1,500/mcL
   • Platelets >100,000/mcL
   • Total bilirubin 1.5 upper limit of normal (ULN)
   • AST (SGOT) / ALT (SGPT) 2.5 ULN
   • Creatinine clearance 60 mL/min
9. Patients must be 18 years of age

Exclusion Criteria:

1. Early discontinuation of TMZ in first line due to treatment related Adverse events (AEs).
2. Second primary malignancy expected to require treatment within a 6 month period (except adequately treated basal cell carcinoma of the skin).
3. Have received treatment within the last 28 days with a drug that has not received regulatory approval for any indication at the time of study entry.
4. Serious concomitant systemic disorders
5. Patients with abnormal sodium, potassium, or creatinine levels grade 2.
6. Patients with prothrombin time/partial thromboplastin time (PT/PTT) or International normalized ratio (INR) above the ULN.
7. Inability to comply with protocol or study procedures.