Advanced Malignant Glioma, Anaplastic Astrocytomas, Glioblastoma Multiforme
Conditions
Keywords
Epidermal Growth Factor Receptor Variant III, EGFRvIII, Glioma, Anaplastic Astrocytomas, Glioblastoma Multiforme, Antibody drug conjugate, brain tumor
Brief summary
This is an open-label, sequential dose exploration study of single agent AMG 595 administered in subjects with recurrent glioblastoma multiforme (GBM) and/or anaplastic astrocytomas (AA). The purpose of the study is to evaluate safety, tolerability, and pharmacokinetics (PK) of AMG 595, and also to evaluate the objective response rate in subjects receiving AMG 595. This study will be conducted in two parts. Part 1 will explore doses of AMG 595 in subjects with recurrent GBM and/or AA. Part 2 (dose expansion) will examine the MTD established in Part 1 in subjects with recurrent GBM.
Detailed description
This study of AMG 595 will be conducted in two parts: Part 1 (dose exploration) and Part 2 (dose expansion). Part 1 of the study is in subjects with recurrent glioblastoma multiforme (GBM) and/or anaplastic astrocytomas (AA), and Part 2 is examining the MTD in subjects with recurrent GBM. Approximately 30-40 subjects may be enrolled in Part 1, and up to 36 subjects may be enrolled in Part 2. The dose of AMG 595 utilized in Part 2 will be dependent upon data obtained in Part 1 of the study.
Interventions
DRUGAMG 595
AMG 595 is an antibody drug conjugate that binds to EGFRvIII.
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Karnofsky performance score \> or = 70% * Must have pathologically documented, and definitively diagnosed recurrent WHO Grade IV advanced malignant glioblastoma multiforme (Part 1 and Part 2) and/or WHO Grade III anaplastic astrocytoma (Part 1 only). * GBM and/or AA tumors expressing EGFRvIII as assessed on archived tissue by IHC staining of sections containing a minimum of 100 evaluable tumor cells. * Archived tumor tissue from the initial diagnosis or subsequent relapse(s) of Grade IV advanced malignant glioblastoma multiforme or Grade III anaplastic astrocytoma available for submission to central review. * Subjects with recurrent disease (confirmed by MRI and evaluable by Macdonald criteria) at the time of first or second recurrence or progression following initial definitive therapy(s) * QTcF ≤ 470 msec * Hematological function, as follows: Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L, Platelet count ≥ 100 x 10\^9/L, Hemoglobin \> 9 g/dL * Renal function, as follows: Estimated glomerular filtration rate using the Modified Diet in Renal Disease (MDRD) equation \> 45 mL/min/1.73m\^2, Urinary protein quantitative value of \< 30 mg/dL in urinalysis or ≤ 1+ on dipstick, unless quantitative protein is \< 500 mg in a 24 hr urine sample
Exclusion criteria
* History of central nervous system bleeding as defined by stroke or intraocular bleed (including embolic stroke) within 6 months before enrollment. * Evidence of acute intracranial / intratumoral hemorrhage, except for subjects with stable grade 1 hemorrhage. * Peripheral sensory neuropathy \> Grade 2. * Clinically significant ECG changes which obscure the ability to assess the PR, QT, and QRS interval; congenital long QT syndrome. * Recent infection requiring intravenous anti-infective treatment that was completed ≤ 14 days before enrollment. * Received radiation therapy within 12 weeks before enrollment or has not recovered from the toxic effects of such therapy. * For Part 1 (dose escalation): Treatment with bevacizumab or antiangiogenic therapy within 4 weeks before enrollment, or for Part 2 (dose expansion): any prior treatment with bevacizumab or antiangiogenic therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicity used to estimate the MTD | 28 Days after last subject enrolled of each cohort in Part 1 and every 10, 20 and 30 subject enrolled in part 2 (if available) |
| Clinically significant or > or = to Grade 3 CTCAE changes in safety laboratory tests, physical exams, ECGs or vital signs | 28 Days after last subject enrolled of each cohort in Part 1 and every 10, 20 and 30 subject enrolled in part 2 (if available) |
| PK Parameters: Cmax, Cmin, and if feasible half life - 8 time points up to 6 weeks | 28 Days after last subject enrolled of each cohort in Part 1 and every 10, 20 and 30 subject enrolled in part 2 (if available) |
| Objective response in GBM tumors as assessed by Macdonald criteria | 3 years |
Secondary
| Measure | Time frame |
|---|---|
| Clinical benefit rate | every 6 months |
| Progressive free survival | 3 years |
| Overall survival | 3 years |
| Anti-AMG 595 antibody formation | 3 years |
Countries
Australia, United States
Outcome results
None listed