A Phase 1, Open-Label, Dose Escalation Study of ANG1005 in Patients With Malignant Glioma
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||A Phase 1, Open-Label, Dose Escalation Study of ANG1005 in Patients With Malignant Glioma|
- To characterize the safety and tolerability of intravenously administered ANG1005 in patients with malignant glioma. [ Time Frame: On-going ]
- To identify the maximum tolerated dose (MTD) of ANG1005 in patients with malignant glioma. [ Time Frame: End of dose escalation ]
- To examine the pharmacokinetics (PK) of ANG1005. [ Time Frame: End of study ]
- To confirm the safety and tolerability of ANG1005 at the MTD. [ Time Frame: End of dose escalation ]
- To assess the immunogenicity of ANG1005. [ Time Frame: End of study ]
- To obtain preliminary information about the antitumor activity of ANG1005 in patients with malignant glioma. [ Time Frame: On-going ]
- To obtain preliminary information about whether or not ANG1005 crosses the blood- brain barrier into malignant glioma tumors (Sub-study). [ Time Frame: On-going ]
|Study Start Date:||October 2007|
|Study Completion Date:||March 2010|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
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 glioma.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00539344
|United States, Massachusetts|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Michigan|
|Henry Ford Health System|
|Detroit, Michigan, United States, 48202|
|United States, New York|
|Irving Comprehensive Cancer Center, Columbia University Medical Center|
|New York, New York, United States, 10032|
|United States, Texas|
|University of Texas, MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|UT Health Science Center at the Cancer Therapy and Research Center (CTRC)|
|San Antonio, Texas, United States, 78229|
|United States, Virginia|
|University of Virginia Health System|
|Charlottesville, Virginia, United States, 22908|