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

An Open-Label Pilot Phase 2 Study to Investigate the Preliminary Efficacy and Safety of Aldoxorubicin in Subjects With Unresectable Glioblastoma Whose Tumors Have Progressed Following Prior Treatment With Surgery, Radiation and Temozolomide

This is a pilot study to determine the efficacy and safety of aldoxorubicin in subjects with glioblastoma who have progressed following surgery and prior treatments.

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:

1. Age 18 years or older; male or female

2. 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.

3. Cancer progression after treatment with the following: surgery, radiation therapy and temozolomide as first line treatment with no other therapy prior to tumor recurrence.

   1. Radiographic progression by RANO Working Group Criteria will be confirmed by Imaging Endpoints, a central imaging vendor.
   2. By tumor biopsy if conducted within 4 weeks of randomization.

4. 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.

5. Stable or decreasing dose of corticosteroids for at least 7 days prior to randomization.

6. Capable of providing informed consent and complying with trial procedures.

7. Karnofsky Performance Status 70 or above.

8. ECOG performance status 0-2.

9. Life expectancy 8 or more weeks.

10. 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.

11. Women must not be able to become pregnant for the duration of the study.

12. Women of childbearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.

13. Geographically accessible to site, i.e. the ability to come to the study site for each scheduled appointment and evaluation.

Exclusion Criteria:

1. Prior exposure to the an anthracycline.
2. Any therapeutic regimen for treatment of recurrent tumor after first line treatment with surgery, radiation and temozolomide.
3. Prior treatment with bevacizumab or an experimental anti-angiogenic agent.
4. Palliative surgery and/or radiation treatment less than 4 weeks to randomization.
5. Exposure to any investigational agent within 30 days of Randomization.
6. 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.
7. 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.
8. Evidence of CNS hemorrhage CTCAE ≥ grade 2 on baseline MRI.
9. Clinically evident congestive heart failure > class II of the NYHA guidelines.
10. Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrythmias classified as Lown III, IV or V.
11. History or signs of active coronary artery disease with or without angina pectoris.
12. Serious myocardial dysfunction defined as ultrasound-determined LVEF < 45% of predicted institutional normal value.
13. Baseline ATc>470 msec and/or previous history of QT prolongation.
14. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals, or anti-fungals.
15. History of HIV infection.
16. Major surgery, except diagnostic tumor biopsy, within 4 weeks of randomization.
17. Any condition that might interfere with the subject's participation in the study or in the evaluation of the study results.
18. Any condition that is unstable and could jeopardize the subject's participation in the study.