Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01290263 | Amgen 386 for Recurrent Glioblastoma | PHASE1 | COMPLETED | 48 | — | — | Dec 1, 2010 | Jan 1, 2017 | Jul 2, 2017 | 6 | United States |
PFS6 is the proportion of patients remaining alive and progression-free at 6-months from study entry. Progressive disease was established based on Response Assessment in Neuro-Oncology (RANO) criteria (Wen et al JCO 2010). RANO criteria has 5 potential categories: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive disease (PD) and Unknown status. CR: disappearance of all enhancing lesions, stable or improved non-enhancing lesions, and stable or improved clinically. PR: \>= 50% decrease in sum of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, stable or improved non- enhancing lesions, and stable or improved clinically. PD: \> 25% increase in sum of perpendicular diameters of all measurable enhancing lesions, significant increase of non-enhancing lesions, any new lesions, clear clinical deterioration, failure to return for evaluation due to death or deteriorating condition. SD: d
The MTD of weekly AMG 386 intravenously (IV) in combination with bevacizumab 10 mg/kg intravenously (IV) on days 1 and 15 of each 28 day cycle is determined by the number of participants who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached but the highest dose received may be the Recommended Phase II Dose (RP2D).
A DLT is defined as an adverse event that (a) is related to the AMG 386 and/or bevacizumab with an attribution of possible, probable, or definite, and (b) occurs during and/or begins during the first 28 days of the study treatment, and (c) meets any of the following criteria: \>= grade 3 thrombocytopenia; grade 4 neutropenia lasting \> 7 days; grade 4 anemia lasting \> 7 days despite transfusion or growth factors; febrile neutropenia if ANC\<0.5x10\^9/L; clinically significant grade 3 non-hematologic toxicity despite maximal medical therapy lasting \> 7 days, with the exception of grade 3 proteinuria which was considered a DLT if lasting \> 14 days; grade 3 non-hematologic toxicity resulting in study drug discontinuation; grade 4 non-hematologic toxicity; \>= grade 1 new CNS hemorrhage; \>= grade 2 non-CNS hemorrhage.
| Arm | Type | Description |
|---|---|---|
| Amgen 386 | EXPERIMENTAL | Cohort A will assess recurrent Glioblastoma Multiforme (GBM) patients who receive AMG 386 monotherapy at 30mg/kg every week. As of August 1, 2013, Cohort A was closed to new accrual following early interim analysis of first 10 participants enrolled on study. None of these patients had achieved stable disease or response at their initial evaluation after 1-2 months of study therapy. Therefore, study investigators and sponsor agreed that the level of single-agent anti-tumor activity associated with AMG386 for recurrent glioblastoma patients is most likely insufficient to satisfy the stopping rule for low efficacy outlined in Section 14.5 for Cohort A. |
| Amgen 386 and Bevacizumab | EXPERIMENTAL | Cohort B will assess recurrent Glioblastoma Multiforme(GBM) patients who receive AMG 386 plus bevacizumab. Because the maximum tolerated dose of this combination therapy has not yet been established, a 3x3 Phase I study was used to determine the maximum tolerated dose. As of June 6, 2014, the MTD was determined to be AMG386 30 mg/kg administered intravenously every week(dose level +1) in combination with bevacizumab at 10mg/kg administered intravenously every other week. As of July 25, 2014 the Cohort B, Phase II portion of the study was opened to accrual. |
| Name | Type | Description |
|---|---|---|
| Amgen 386 | DRUG | For Cohort A, AMG 386 will be administered intravenously at 30 mg/kg every week. For Cohort B Phase I, AMG 386 will be administered intravenously at beginning at starting dose level of 15 mg/kg every week. For Cohort B Phase II, AMG 386 will be administered intravenously at the maximum tolerated dose determined in the Phase I portion of the study every week. |
| Bevacizumab | DRUG | The dose of bevacizumab will be 10 mg/kg and will be administered intravenously every other week. |
Inclusion Criteria * Signed informed consent approved by the Institutional Review Board prior to participant entry * Age ≥ 18 years. * Karnofsky ≥ 70% * Participant must be able and willing to comply with study and/or follow-up procedures Participants must have histologically confirmed diagnosis of...