Inclusion Criteria

Inclusion criteria

1. Be informed of the nature of the study and have provided written informed consent

2. At least 18 years of age

3. ECOG performance of 0, 1, or 2, or KPS (Karnofsky performance status) ≥ 60.

4. Pathological verification of a WHO grade 4 astrocytoma (glioblastoma or gliosarcoma),
or WHO Grade 3 anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic
oligoastrocytoma, or anaplastic ependymoma.

5. Documented recurrent glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic
oligodendroglioma, anaplastic oligoastrocytoma, or anaplastic ependymoma after at
least one failed treatment of chemotherapy and radiation

6. Expected survival of at least 3 months

7. At least 2-weeks from cytoreductive surgery, if performed, 4-weeks from bevacizumab
or other chemotherapy (6-weeks if prior chemotherapy was nitrosourea) and 12-weeks
from completion of radiotherapy.

8. Ability to undergo MRI scanning without and with imaging dye on a periodic basis as
defined in the protocol

9. At least seven (7) days off of medications with induce CYP2C9 and CYP3A4 before
administration of the first dose of AXL1717

10. Preserved major organ functions, i.e: Blood leukocyte count ≥ 3.0 x 109/L Blood
absolute neutrophil count ≥ 1.5 x 109/L Blood platelet count ≥ 100 x109/L Blood
hemoglobin ≥ 100 g/L (transfusions are allowed) Plasma total bilirubin level ≤ 1.5
times the upper institutional limit (ULN) of the ‖normal‖ (i.e. reference) range
Plasma AST (aspartate aminotransferase) or ALT ≤ 2.5 times upper institutional limit
(ULN) of the ‖normal‖ range Plasma creatinine ≤ 1.5 times upper institutional limit
(ULN) of the ‖normal‖ range 12-lead ECG with normal tracings; or changes that are not
clinically significant and do not require medical intervention, and QTc < 500 ms At
least seven (7) days off of medications which inhibit or induce CYP2C9 or CYP3A4
before first study treatment day

Exclusion criteria

1. Ongoing infection or other major recent or ongoing disease that, according to the
Investigator, poses an unacceptable risk to the patient

2. Grade 3 or higher constipation within the past 28 days or grade 2 constipation within
the past 14 days before randomization. (Patients with grade 2 constipation within the
past 14 days could be re-screened if constipation decreases to ≤ grade 1 with optimal
management of constipation.)

3. Coexisting uncontrolled medical condition, including, but not limited to, active
cardiac disease and significant dementia

4. Hepatitis B or Hepatitis C, or HIV infection requiring anti-retroviral therapy

5. Active malignancy other than basal cell skin cancer

6. Other active malignancy during the previous 3 years

7. Major surgical procedure within 4 weeks

8. Prior stereotactic or gamma knife radiosurgery or proton radiation, unless
unequivocal progression by functional neuro-imaging (PET, dynamic MRI, MRS, SPECT) or
by re-operation with documented histologic confirmation of recurrence.

9. Prior anti-tumor therapy, as follows: at least 12-weeks from radiation therapy; at
least 4-weeks from prior treatment with temozolomide or bevacizumab, 6-weeks from
BCNU or CCNU.

10. Women of child bearing potential (WOCBP) who do not consent to using acceptable
methods of birth control (oral contraceptives, IUD). For purposes of this study,
WOCBP include any female who has experienced menarche, who has not undergone tubal
ligation, and who is not postmenopausal. Post menopause is defined as: amenorrhea ≥
12 consecutive months without another cause.

11. Medically uncontrolled Type 1 or Type 2 diabetes mellitus

12. Pregnancy or lactation

13. Current participation in any other investigational clinical trial within 4-weeks.

14. Eastern Cooperative Oncology Group (ECOG) performance status > 2 after optimization
of medications (See Appendix 4) or KPS < 60

15. Anticipated Life expectancy less than 3 months

16. Contraindications to the investigational product or known or suspected
hypersensitivity

17. Patients who must take concomitant medications which induce or are potent inhibitors
of CYP2C9 or sensitive substrates of CYP3A4 with narrow therapeutic range may not
participate (see Appendix 7)

18. Lack of suitability for participation in the trial, for any reason, as judged by the
Investigator.