Phase II NKTR-102 In Bevacizumab-Resistant High Grade Glioma

Inclusion Criteria: * Pathologically proven high-grade glioma (WHO III or IV) with astrocytic component and must be in recurrence after treatment with bevacizumab * Patients must have received conventional radiation therapy of total radiation dosage (ranging from 5400 to 6000 cGy administered in daily fractions of 150 to 200 cGy over 6 weeks) with concurrent temozolomide. Patients must have received bevacizumab and be in recurrence after bevacizumab treatment. * Patients must be at least 28 days from last administration of cytotoxic chemotherapy and at least 14 days from the last administration of bevacizumab. * Patients must be \>18 years of age. * Patients must have a life expectancy \> 6 weeks * Patients must have a Karnofsky Performance Score (KPS) \>=50 * If female, patients of childbearing potential must have a negative serum beta-hCG pregnancy test and must agree to use hormonal or barrier birth control with spermicidal gel to avoid pregnancy during the study * Adequate organ function (obtained within 14 days prior to randomization and analyzed by the central laboratory) as evidenced by: 1. Absolute neutrophil count (ANC) \>=1.5 X 10\^9/L without myeloid growth factor support for 7 days preceding the lab assessment; 2. Hemoglobin (Hgb) \>= 9 g/dL (90 g/L); \< 9 g/dL (\< 90 g/L) is acceptable if hemoglobin is corrected to \>= 9 g/dL (90 g/L) as by growth factor or transfusion prior to randomization; 3. Platelet count \>=100 X 10\^9/L without blood transfusions for 7 days preceding the lab assessment; 4. Bilirubin \<= 1.5 X upper limit of normal (ULN), except for patients with documented history of Gilbert's disease; 5. Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) \<= 2.5 X ULN 6. Alkaline phosphatase (AP) \<= 3 X ULN 7. Serum creatinine \<= 1.5 mg/dL (133 µmol/L) or calculated creatinine clearance \>= 50 mL/min (using Cockcroft-Gault formula); 8. Women of childbearing potential (WCBP): negative serum pregnancy test (this test is required of all women unless post-menopausal, defined as 12 consecutive months since last regular menses, or surgically sterile). * Patients must be willing and able to comply with the protocol and provide written informed consent prior to study-specific screening procedures. Exclusion Criteria: Patients who meet any of the following criteria must not be permitted entry to the study. * Patients who have had chemotherapy within 28 days, radiotherapy within 28 days, biological therapy within 14 days, and investigational therapy within 21 days prior to first dose of experimental drug. * Patients who have received prior treatment for cancer with a camptothecin derivative (eg, irinotecan, topotecan, and investigational agents including but not limited to exatecan, rubitecan, gimatecan, karenitecan, SN38 investigational agents, EZN-2208, SN-2310, and AR-67). * Patients with the following co-morbid disease or incurrent illness: 1. Patients with chronic or acute GI disorders resulting in diarrhea of any severity grade; patients who are using chronic anti-diarrheal supportive care (more than 3 days/week) to control diarrhea in the 28 days prior to first dose of investigational drug. 2. Patients with known cirrhosis diagnosed with Child-Pugh Class A or higher liver disease. 3. Prior malignancy except for non-melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 3 years prior to first dose of investigational drug. 4. Severe/uncontrolled inter-current illness within the previous 28 days prior to first dose of investigational drug. 5. Significant known cardiovascular impairment (NYHA CHF \> grade 2, unstable angina, myocardial infarction within the previous 6 months prior to first dose of investigational drug, or existing serious cardiac arrhythmia). 6. Patients who require daily use of oxygen supplementation in the 28 days prior to first dose of investigational drug. 7. Any other significant co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation. * Patients with a known allergy or hypersensitivity to any of the components of the investigational therapy, including PEG or topoisomerase inhibitors. * Patients receiving the following medications at the time of first dose of investigational drug: * Pharmacotherapy for hepatitis B or C, tuberculosis, or HIV. * enzyme inducing anti-epileptic medications (EIAEDs) * other chemotherapy, other investigational agents , or biologic agents for * the treatment of cancer including antibodies(eg, bevacizumab, * trastuzumab, or pertuzumab) or any investigational agent(s). * Pregnant or nursing patients will be excluded from the study. * Patients receiving active treatment for HIV will be excluded from this study because non-nucleoside reverse transcriptase inhibitors, protease inhibitors and maraviroc (a CCR5-antagonist) are extensively metabolized by the cytochrome P450 system. Interactions with these drugs may induce or inhibit irinotecan or SN38 metabolism, leading to over or under-dosing.