A Multi-center, Open Label, Two Part, Dose Escalation Study to Determine the Tolerability of Interferon-Beta Gene Transfer (BG00001) in the Treatment of Recurrent or Progressive Grade III and Grade IV Gliomas
1. Must be greater than or equal to 18 years of age.
2. Subjects must have histologically proven GBM, AA, AMO, malignant astrocytoma NOS or
gliosarcoma and recurrent or progressive tumor following prior treatment.
3. Tumor must be amenable to radical resection, and resection must be clinically
4. Must have an ECOG performance status of 0-2.
5. Must be on anticonvulsant therapy, and must have therapeutic serum levels within 2
weeks prior to Day 1, if therapeutic levels are defined for the anticonvulsant being
1. Abnormal blood tests exceeding any of the limits defined below:
- Alanine transaminase (ALT) > four times (4X) the upper limit of normal (ULN).
- Aspartate transaminase (AST) > 4X the ULN.
- Total bilirubin >1.5 mg/dL.
- Absolute neutrophil count <1,500 cells/mm3.
- Platelet count <100,000 cells/mm3.
- Serum creatinine >2X ULN.
- Prothrombin time (PT) >2 seconds above the ULN.
- Serum sodium (Na) <125 mEq/L or >150 mEq/L.
- Serum potassium (K) <3.5 mEq/L or > 5.5 mEq/L.
2. Brainstem, or optic chiasm involvement of tumor.
3. Uncontrolled seizure disorder.
4. History of a new diagnosis or treatment of an invasive malignancy other than Grade
III or Grade IV Glioma within 5 years of enrollment. Curatively treated subjects with
a history of basal cell or squamous cell carcinoma of the skin, superficial
transitional cell carcinoma of the bladder, and non-invasive carcinoma of the uterine
cervix are not excluded.
5. Treatment with radiation therapy, including interstitial radiation or radiosurgery,
must be completed at least 8 weeks prior to Day 1.
6. Treatment with nitrosoureas must be completed at least 6 weeks prior to Day 1.
Treatment with other chemotherapeutic agents must be completed at least 4 weeks prior
to Day 1.
7. Treatment with any investigational drug or approved therapy for investigational use
must be completed at least 4 weeks prior to Day 1.
8. History of intolerance to corticosteroids that would preclude use during this study,
or history of any medical condition that precludes the use of corticosteroids.
9. Any prior treatment with a gene delivery vector, or an adenovirus therapeutic.
10. Women of child bearing potential must have a negative serum pregnancy test.
11. Women who are not postmenopausal, surgically sterile, or willing to practice
effective contraception during the study. Men who are not surgically sterile or
willing to practice effective contraception during the study.
12. Nursing mothers, pregnant women and women planning to become pregnant while on study.
13. Previous treatment with BG00001.