Phase 2 Study to Investigate the Efficacy and Safety of Aldoxorubicin in Subjects With Glioblastoma

This is a second line open-labeled pilot phase 2 study in subjects with glioblastoma whose tumors have progressed following prior treatment with surgery, radiation and Temozolomide. Patients who have received avastin as a second-line treatment are not eligible for this study.

Inclusion criteria

• Age 18 years or older; male or female
• Histologically or cytologically confirmed unresectable GBM. Subjects with recurrent disease whose prior pathology demonstrated GBM will not need to be re-biopsied. Subjects with prior low-grade glioma or anaplastic glioma are eligible if histological assessment demonstrates transformation into GBM.
• Cancer progression after treatment with the following: surgery, radiation therapy and temozolomide as first line treatment with no other therapy prior to tumor recurrence.

• Radiographic progression by RANO Working Group Criteria will be confirmed by Imaging Endpoints, a central imaging vendor.
• By tumor biopsy if conducted within 4 weeks of randomization.
• An interval of at least 12 weeks after last dose of radiation and temozolomide is required, unless cancer progression is proven by diagnostic tumor biopsy. If temozolomide is being used in a maintenance phase, there must be a 28-day washout period prior to Randomization.
• Stable or decreasing dose of corticosteroids for at least 7 days prior to randomization.
• Capable of providing informed consent and complying with trial procedures.
• Karnofsky Performance Status 70 or above.
• ECOG performance status 0-2.
• Life expectancy 8 or more weeks.
• Measurable tumor lesions according to RANO working Group Criteria.

a. In the case that there is "non-measurable" disease due to a radical surgical resection during screening, the subject still qualifies if Inclusion #3(b) is met.

• Women must not be able to become pregnant for the duration of the study.
• Women of childbearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.
• Geographically accessible to site, i.e. the ability to come to the study site for each scheduled appointment and evaluation.

Exclusion criteria

• Prior exposure to the an anthracycline.
• Any therapeutic regimen for treatment of recurrent tumor after first line treatment with surgery, radiation and temozolomide.
• Prior treatment with bevacizumab or an experimental anti-angiogenic agent.
• Palliative surgery and/or radiation treatment less than 4 weeks to randomization.
• Exposure to any investigational agent within 30 days of Randomization.
• History of other malignancies (except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix) unless documented free of cancer for 3 or more years.
• Laboratory values: screening serum creatinine > 1.5xULN, ALT > 2.5xULN, total bilirubin > 1.5xULN, ANC < 1500/mm3, platelet concentrations < 100,000/mm3, absolute lymphocyte count < 1000/mm3, hematocrit level < 27% for females or < 30% for males, serum albumin ≤ 2.5 g/dL, PT/INR 1.5xULN or >3xULN on anticoagulant with no evidence of active bleeding.
• Evidence of CNS hemorrhage CTCAE ≥ grade 2 on baseline MRI.
• Clinically evident congestive heart failure > class II of the NYHA guidelines.
• Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrythmias classified as Lown III, IV or V.
• History or signs of active coronary artery disease with or without angina pectoris.
• Serious myocardial dysfunction defined as ultrasound-determined LVEF < 45% of predicted institutional normal value.
• Baseline ATc>470 msec and/or previous history of QT prolongation.
• Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals, or anti-fungals.
• History of HIV infection.
• Major surgery, except diagnostic tumor biopsy, within 4 weeks of randomization.
• Any condition that might interfere with the subject's participation in the study or in the evaluation of the study results.
• Any condition that is unstable and could jeopardize the subject's participation in the study.