Cancer Stem Cell High-Throughput Drug Screening Study

Inclusion Criteria: Determined at pre-screening: * A histological diagnosis of GBM \[WHO grade IV\]. * Subjects ≥18 years of age * Signed informed consent for tumor collection prior to initiation of any study-specific procedure. The patient or the patient's legal authorized representative must be able to provide written informed consent (ICF) and understand the potential risks and benefits from study enrollment and treatment * Patients must have a life expectancy of \>12 weeks Determined at or around surgery, and prior to performing HTS: * Patients must have a surgically accessible tumor with the intent for a gross or near total resection of the tumor mass (GBM, WHO grade IV) * Collection of sufficient tumor material for processing CSCs Determined at or around tumor recurrence, and after completion of HTS: • Disease progression following radiation and TMZ therapy (as defined by RANO criteria (45); Appendix 3). Unlimited relapses are allowed, provided the functional status and other eligibility criteria for enrollment are met Determined at baseline: * Signed informed consent for CSC/HTS based therapy prior to initiation of any study-specific procedure or treatment. The patient or the patient's legal authorized representative must be able to provide written informed consent (ICF) and understand the potential risks and benefits from study enrollment and treatment * Patients must have a KPS rating of ≥70 (see Appendix 4: Karnofsky Performance Scale) * Patients must have recovered from the toxic effects of prior therapy to \< Grade 2 toxicity per NCI CTCAE version 4 (Appendix 6) prior to Day 1 of Cycle 1. The minimum duration required between prior therapy and initiation of study drug treatment is as follows: * At least 12 weeks from completion of radiation therapy except if there is unequivocal evidence for tumor recurrence (such as histological confirmation) in which case at least 4 weeks from completion of radiation will suffice * 4 weeks from prior cytotoxic chemotherapy * 4 weeks from prior experimental drug * 6 weeks from nitrosoureas * 3 weeks from procarbazine * 1 week for non-cytotoxic agents. * Subjects must have adequate renal, hepatic and bone marrow function based on screening laboratory assessments. Baseline hematologic studies and chemistry and coagulation profiles must meet the following criteria: * Hemoglobin (Hgb)\> 8 g/dL * Absolute Neutrophil Count (ANC) \> 1,000/mm3 * Platelet count \> 100,000/mm3 * Creatinine \< 2 mg/dL * Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) \< 3x upper limit of normal (ULN) * Patients of childbearing potential must agree to use an adequate method of contraception for the duration of the study, and for 90 days following discontinuation of study drugs * Females of childbearing potential must have a negative pregnancy test * Patients must be negative for HIV, Hepatitis B and C * Patients are cooperative and able to complete all the assessment procedures. Exclusion Criteria: * Any condition, including the presence of clinically significant laboratory abnormalities, which places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study * Active infection, (including known Acquired Immunodeficiency Syndrome (AIDS) and Hepatitis C) within 3 days prior to the study enrollment * Diseases or conditions that obscure toxicity or dangerously alter drug metabolism * Serious intercurrent medical illness (e.g., symptomatic congestive heart failure) * Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from providing informed consent unless they have a legal authorized representative that can consent on their behalf * Inadequately controlled hypertension (defined as systolic blood pressure \>140 mmHg and/or diastolic blood pressure \>90 mmHg) * Prior history of hypertensive crisis or hypertensive encephalopathy * New York Heart Association (NYHA) Grade II or greater congestive heart failure * History of myocardial infarction or unstable angina within 6 months * History of stroke or transient ischemic attack within 6 months * Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months * History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month. * Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). * Grade 2 or higher peripheral neuropathy per NCI CTCAE version 4 * History of abdominal fistula or gastrointestinal (GI) perforation within 6 months. * Serious, non-healing wound, active ulcer, or untreated bone fracture * Allergies to reagents used in this study * Women of child bearing age not willing to use a reliable form of contraception * Pregnancy (positive pregnancy test) or lactation * Patient is positive for HIV, Hepatitis B or C * Concurrent use of enzyme-inducing anti-epileptic drugs (EIAEDs) Patients must discontinue an EIAED at least two weeks prior to starting study drug * Concurrent use of herbal medications * Patient is simultaneously participating in another clinical trial during the Phase 1 (treatment phase) of this study. Patients may enroll/consent in the Phase 0 portion of this study for tissue collection and HTS while being treated with standard of care or clinical trial for newly diagnosed GBM prior to recurrence. Inability or unwilling to comply with protocol or study procedures.