Safety and Efficacy Study of TH-302 CNS Penetration in Recurrent High Grade Astrocytoma Following Bevacizumab

Exclusion Criteria

• •1. The subject is receiving warfarin (or other coumarin derivatives) and is unable to switch to low molecular weight heparin (LMWH) before the first dose of study drug.
• •2. The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible.
• •3. The subject is unable to undergo MRI scan (eg, has pacemaker).
• •4. The subject has received enzyme-inducing anti-epileptic agents within 14 days of study drug (eg, carbamazepine, phenytoin, phenobarbital, primidone).
• •5. The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grade ≤ 1 from AEs (except alopecia, anemia and lymphopenia) due to surgery, antineoplastic agents, investigational drugs, or other medications that were administered prior to study drug.
• •6. The subject has evidence of wound dehiscence
• •7. Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation \<90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause normal tissue hypoxia
• •8. The subject is pregnant or breast-feeding.
• •9. The subject has serious intercurrent illness
• •10. The subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding.
• •11. The subject has received any of the following prior anticancer therapy:
• •* Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy (RIT), or intra-operative radiotherapy (IORT). Note: stereotactic radiosurgery (SRS) is allowed
• •* Antiangiogenic agents whose primary mode of action is through the VEGF signaling within 21 days prior to first dose of study drug (surgical subjects only)
• •* Non-bevacizumab systemic therapy (including investigational agents and small-molecule kinase inhibitors) or non-cytotoxic hormonal therapy (eg, tamoxifen) within 7 days or 5 half-lives, whichever is shorter, prior first dose of study drug
• •* Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21 days prior to first dose of study drug
• •* Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, prior to first dose of study drug
• •* Prior treatment with carmustine wafers
• •* Prior treatment with TH-302