Status: Closed
Activation Date: 2016JAN13
Closing Date: 2018OCT19
Phase: I
Description: A Phase I Study of the mTORC1/mTORC2 Kinase Inhibitor AZD2014 in Patients with Previously Treated Glioblastoma Multiforme
Eligibility: Histologically confirmed glioblastoma multiforme that is recurrent after primary treatment, phase II must have measurable disease according to RANO criteria. ECOG 0-1. Radiation completed >= 4 weeks prior registration; surgery within 21 days (excluding resection). No clinically significant cardiac disease in last 12 months such as (coronary artery bypass graft, angioplasty, vascular stent, MI, congestive heart failure NYHA Grade 2, ventricular arrhythmias requiring continuous therapy, uncontrolled arrhythmias including atrial fibrillation, hemorrhagic or thrombotic stroke). No hepatitis B, hepatitis C, HIV or a prior history of tuberculosis, or diabetes type I or uncontrolled type II. No interstitial lung disease. No GI disease, meningeal or extracranial GBM involvement. No known QT/QTc-prolonging drugs. Stable or decreasing dose of corticosteroids. No enzyme inducing anticonvulsants. No medications that are metabolized by CYP3A4/5 5 and CYP2C8, Pgp (MDR1) and BCRP
Objective: Primary:To determine the recommended phase II dose (RP2D) of AZD2014 in patients receiving standard temozolomide treatment. To estimate the 6 month PFS rate in patients receiving AZD2014 in addition to their standard temozolomide treatment Secondary:To evaluate the plasma levels of AZD2014 alone at the time of resection. To assess the safety and toxicity profile of AZD2014 in patients receiving standard temozolomide treatment. To evaluate potential biomarkers such as PTEN, PI3KCA and other mutations, as well as evidence of pharmacodynamic effects in resected and archival tumour tissue.
Participation: Limited to invited centres
Lay Description: The main purpose of this study is to determine the recommended phase II dose and safety profile of AZD2014 combined with standard temzolomide in patients with previously treated glioblastoma multiforme, and to estimate the 6 month progression-free rate and response in patients receiving AZD2014 in addition to their standard temozolomide treatment for the phase 2 portion. Secondary, to explore potential biomarkers such as PTEN, PI3KCA and other mutations, as well as evidence of pharmacodynamic effects in resected and archival tumour tissue.
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Hide Tissue Samples
| Disease Site | Trial Code | Patients Accrued | Patients - Blocks | Patients - Slides | Patients - Blocks and/or Slides |
| IND | I222 | 15 | 7 | 12 | 13 |
(Core size is 0.6 mm)
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Fluid Samples| Disease Site | Trial Code | Patients Accrued | TMA Blocks | Patients on TMA Blocks |
| IND | I222 | 15 | 0 | 0 |
| Disease Site | Trial Code | Patients Accrued | Patients - Whole Blood | Patients - Cellular Component of Blood | Patients - DNA extracted from Blood | Patients - RNA extracted from Blood | Patients - Plasma | Patients - Serum | Patients - Urine | Patients - Buccal |
| IND | I222 | 15 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 |