Details
Description
Inclusion Criteria
Exclusion Criteria
Details
Title A Phase II, Open-Label, Multi-Center Study of ANG1005 in Patients with Recurrent High-Grade Glioma
IRB ANG 1314
CC 14-1262
Hospital Main Campus
Phase Phase 2
Disease Brain, Glioblastoma, Glioma
Drug ANG1005
Description
Primary Objectives- To determine the objective response rate (ORR) in bevacizumab-naive recurrent GBM patients (Arm 1)
- To determine the rate of PFS3 in the bevacizumab-refractory recurrent GBM patients (Arm 2)
- To determine the ORR in recurrent AG patients (Arm 3)
- To determine the ORR in Arm 2
- To determine the number of patients without progression at 3, 6 and 12 months in Arms 1 and 3
- To determine the number of patients without progression at 6 and 12 months in Arm 2
- To determine the median progression-free survival in each arm
- To determine the median duration of response in each arm
- To determine the median overall survival in each arm
- To determine the safety and tolerability
- To determine the plasma pharmacokinetic profile
- To assess the immunogenicity of ANG1005
- ORR , PFS3 and PFS6, as determined by an Independent Radiology Reviewer
- To evaluate changes in neurocognitive function
- To explore molecular correlates of clinical outcome with LRP-1 receptor status, protease levels and potential glioma biomarkers from tumor specimens.
Inclusion Criteria
- Adult patients (≥ 18 years) who provide written informed consent.
- Histopathologically-confirmed, GBM and GBM variants (e.g., gliosarcoma, glioblastoma multiforme with oligodendroglial components (GBMO), etc.), anaplastic glioma (WHO grade III: astrocytoma or oligodendroglioma including anaplastic oligoastrocytomas).
- Radiologically confirmed recurrent and bi-dimensionally measurable disease per RANO criteria with at least one target lesion not previously treated with SRS.
- Neurologically stable, defined as receiving stable doses of corticosteroids and anticonvulsants (not EIAEDs) for ≥ 1 week prior to first treatment at Cycle 1, Day 1.
- For bevacizumab-refractory patients, radiologic demonstration of tumor progression during bevacizumab therapy.
- Karnofsky Performance Status (KPS) score ≥ 80 at screening and at Cycle 1, Day 1.
- Adequate laboratory test results for organ systems, as follows:
- Hematology within 3 days prior to first dose of ANG1005 (Cycle 1, Day 1)
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Hgb ≥ 9.0 g/dL
- Platelets ≥ 100 x 109/L
- Serum Chemistry within 7 days prior to the first dose of ANG1005 (Cycle 1, Day 1)
- Total bilirubin < 1.6 mg/dl or < the upper limit of normal (ULN). Serum direct bilirubin ≤ ULN for patients with documented Gilbert's syndrome.
- Aspartate aminotransferase (AST; SGOT) and alanine aminotransferase (ALT; SGPT) < 2.5 x ULN.
- Alkaline phosphatase < 2.5 x ULN
- Serum creatinine < 1.5 mg/dL or creatinine clearance ≥ 45 mL/min
- Hematology within 3 days prior to first dose of ANG1005 (Cycle 1, Day 1)
- Expected survival of at least 3 months.
- Male and female patients who are not surgically sterile or post-menopausal must agree to use reliable methods of birth control for the duration of the study and for 90 days after the last administration of study treatment. Male partners of female patients should use condoms for the duration of the study, and for 90 days after the last administration of study treatment.
Exclusion Criteria
- More than three relapses.
- Radiotherapy within 3 months of Cycle 1, Day 1. Surgery, chemotherapy and/or investigational agents within 4 weeks or 5 half lives (whichever is shorter) of Cycle 1, Day 1. Nitrosoureas within 6 weeks of Cycle 1, Day 1. Biologic therapy and/or immunotherapy within 1 week of Cycle 1, Day 1 (except for bevacizumab, which can be continued in Arm 2). Temozolomide within 3 weeks of Cycle 1, Day 1.
- Therapy with bevacizumab within 4 weeks prior to Cycle 1, Day 1 for recurrent WHO grade III anaplastic glioma patients (Arm 3).
- Prior therapy with bevacizumab for bevacizumab-naive patients (Arm 1).
- Prior treatment with ANG1005/GRN1005.
- Evidence of significant intracranial hemorrhage, as assessed by the Investigator.
- Exposure to P450 CYP 3A4 or 2C8 enzyme-inducing antiepileptic drugs within 2 weeks prior to Cycle 1, Day 1.
- Current use of St. John's wort and grapefruit/grapefruit juice within 1 week prior to Cycle 1, Day 1.
- Pregnancy or lactation.
- NCI CTCAE v4.0 Grade ≥ 2 neuropathy.
- Inadequate bone marrow reserve (absolute neutrophil count < 1.5 x 109/L, platelet count < 100 x 109/L, and/or requiring regular blood transfusions to maintain hemoglobin > 9 g/dL) prior to Cycle 1, Day 1.
- Any evidence of severe or uncontrolled diseases (e.g., unstable or uncompensated respiratory, cardiac (including arrhythmias), hepatic and/or renal diseases), as assessed by Investigator.
- Patients with the presence of an infection including abscess or fistulae, or known infection with hepatitis C or B or HIV.
- Known severe hypersensitivity or allergy to paclitaxel or any of its components.