A Phase 1, Open-Label, Dose Escalation Study of ANG1005 in Patients With Malignant Glioma
This is a phase 1, multi-centre, sequential cohort, open-label, dose-escalation study of the
safety, tolerability, and PK of ANG1005 in patients with recurrent or progressive malignant
glioma. ANG1005 will be given by IV infusion once every 21 days (1 treatment cycle). Each
patient will participate in only 1 dose group and will receive up to 6 cycles. Patients may
receive additional cycles of ANG1005 if there is no evidence of tumor progression, there is
recovery to ≤Grade 1 or baseline nonhematologic, ANG1005-related toxicity (except alopecia),
the absolute neutrophil count is ≥1.5 x 109/L, and the platelet count is ≥100 x 109/L.
Initially, cohorts of 1 - 3 patients will be enrolled into each dose group. Dose escalation
by dose doubling will be done for the first 3 dose groups followed by a modified Fibonacci
dose escalation scheme with increases of 67%, 50%, 40% and 33% thereafter. If > 1 patient in
a cohort experience an emergent ≥ Grade 2 drug-related toxicity during the first treatment
cycle, then a minimum of 3 patients will be enrolled into that, and all subsequent cohort(s)
and dose doubling will be stopped if applicable.
If > 1 patient in a cohort experience a dose limiting toxicity (DLT) during the first
treatment cycle, defined as any of the following that are both treatment-emergent and at
least possibly related to ANG1005: i) Any Grade 3 or 4 nonhematologic toxicity, ii) Febrile
neutropenia, iii) Grade 4 neutropenia of ≥7 days duration, and/or iv) Any Grade 4
thrombocytopenia, then dose escalation will stop and prior doses will be explored as the
maximum tolerated dose (MTD), that dose-level at which ≤1 of 6 patients in a cohort develop
an emergent DLT).
Once the MTD is established, approximately 14 patients will be enrolled at that dose-level
in order to further assess the safety and tolerability of ANG1005, the PK profile of ANG1005
at the MTD, and the preliminary anti-tumor activity of ANG1005 in patients with malignant
Approximately 8 additional patients who are scheduled for debulking surgery for recurrent
disease may be enrolled into a separate sub-study to obtain preliminary information about
whether or not ANG1005 crosses the blood-brain barrier into malignant glioma tumors. These
patients will receive ANG1005 prior to surgery at the dose level established to be safe and
tolerable at that time and may continue to receive additional cycles of ANG1005 following
surgery, if appropriate.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label
To characterize the safety and tolerability of intravenously administered ANG1005 in patients with malignant glioma.
United States: Food and Drug Administration
|Henry Ford Health System||Detroit, Michigan 48202|
|Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|University of Texas, MD Anderson Cancer Center||Houston, Texas 77030|
|University of Virginia Health System||Charlottesville, Virginia 22903|
|Irving Comprehensive Cancer Center, Columbia University Medical Center||New York, New York 10032|
|UT Health Science Center at the Cancer Therapy and Research Center (CTRC)||San Antonio, Texas 78229|