1. Newly diagnosed, histologically confirmed GBM WHO Grade IV (any wildtype or mutant or
gene type, except gliosarcoma), non-resectable or partially resected or resected.
2. Age 20
3. Karnofsky Performance Status (KPS) ≥ 60.
4. Expected life expectancy ≥16 weeks.
5. Stable or decreasing corticosteroids (5 mg/day dexamethasone or equivalent) within 5
days before the first dose of ADI-PEG 20.
6. No prior systemic therapy, immunotherapy, investigational agent, or radiation therapy.
7. Recovered from any prior surgery and no major surgery within 2 weeks of initiating
treatment (other than GBM surgery). Surgery for placement of vascular access devices
8. Female subjects and male subjects must be asked to use appropriate contraception for
both the male and female for the duration of the study. Male partners of female
subjects and female partners of male subjects must agree to use two forms of
contraception or agree to refrain from intercourse for the duration of the study if
they are of childbearing potential. Females of childbearing potential must not be
pregnant at the start of the study, and a serum human chorionic gonadotropin (HCG)
pregnancy test must be negative before entry into the study. If positive HCG pregnancy
test, further evaluation to rule out pregnancy must be performed according to GCP
before this subject is deemed eligible. Females not of childbearing potential must be
post-menopausal (defined as cessation of regular menstrual period for at least 12
9. Informed consent must be obtained prior to study initiation.
10. No concurrent investigational studies are allowed.
11. Absolute neutrophil count (ANC) ≥ 1500/μL.
12. Platelets ≥ 100,000/μL.
13. Serum uric acid ≤ 8 mg/dL (with or without medication control).
14. Creatinine clearance must be ≥ 40 mL/min/1.73 m2 (calculated using the Cockcroft-Gault
equation: calculated creatinine clearance = (140-age (yrs)) × body weight (kg) (×0.85
if female) / 72 × serum creatinine (mg/dl).
15. Total bilirubin ≤ 2 x upper limit of normal.
16. ALT and AST ≤ 3 x upper limit of normal, unless liver metastases present then ≤ 5 x
upper limit normal.
1. Serious infection requiring treatment with systemically administered antibiotics at
the time of study entrance, or an infection requiring systemic antibiotic therapy
within 7 days prior to the first dose of study treatment.
2. Pregnancy or lactation.
3. Expected non-compliance.
4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure (New York Heart Association Class III
or IV), cardiac arrhythmia, or psychiatric illness, social .
5. Subjects with history of another primary cancer, including co-existent second
malignancy, with the exception of: a) curatively resected non-melanoma skin cancer; b)
curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no
known active disease present or in the opinion of the investigator will not affect
6. Subjects who had been treated with ADI-PEG 20 previously.
7. History of uncontrolled seizure disorder not related to underlying cancer.
8. Known HIV positivity, or active hepatitis B infection, or active hepatitis C infection
(testing not required).
9. Allergy to pegylated compounds.
10. Allergy to E. coli drug products (such as GMCSF).
11. Allergy to TMZ or any of its components.
12. History of hypersensitivity to dacarbazine.
13. Placement of Gliadel wafer at surgery.
14. Having a co-existing condition requiring systemic treatment with either
corticosteroids or immunosuppressive medication.