Phase I study of non-pegylated liposomal doxorubicin in children with recurrent/refractory high-grade glioma

2015 ◽  
Vol 76 (2) ◽  
pp. 425-432 ◽  
Author(s):  
Pascal Chastagner ◽  
Bénédicte Devictor ◽  
Birgit Geoerger ◽  
Isabelle Aerts ◽  
Pierre Leblond ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
High Grade Glioma ◽  
High Grade

scholarly journals ACTR-59. A PHASE 1 STUDY OF BPM31510 PLUS VITAMIN K IN SUBJECTS WITH HIGH-GRADE GLIOMA THAT HAS RECURRED ON A BEVACIZUMAB-CONTAINING REGIMEN

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi27-vi27
Author(s):  
Lawrence Recht ◽  
Reena Thomas ◽  
Sophie Bertrand ◽  
Priya Yerballa ◽  
Gordon Li ◽  
...  
Keyword(s):  
Phase I ◽  
Vitamin K ◽  
Phase I Study ◽  
Phase 1 ◽  
High Grade Glioma ◽  
High Grade ◽  
Open Label ◽  
Open Label Phase ◽  
Grade 3

Abstract BACKGROUND High-grade gliomas (HGG) are characterized by dysregulated metabolism, utilizing glycolysis for energy production to support unrestricted growth. BPM 31510, an ubidecarenone (coenzyme Q10) containing lipid nanodispersion, causes a switch in cancer energy sourcing from glycolysis towards mitochondrial oxidative phosphorylation in vitro, reversing the Warburg effect and suggesting potential as an anti-tumor agent. The current study is a phase I study of BPM31510 + vitamin K in GB with tumor growth after bevacizumab (BEV). METHODS This is an open-label phase I study of BPM31510 continuous infusion with weekly vitamin K (10mg IM) in HGG patients using an mTPI design, starting at 110mg/kg, allowing for a single dose de-escalation and 2 dose-escalations. Patients had received first-line ChemoRadiation and were in recurrence following a BEV containing regimen. RESULTS 9 eligible and evaluable patients completed the 28 day DLT period. 8 patients had primary GB, 1 had anaplastic astrocytoma with confirmed pathologic transformation to GB. Median age was 55 years (27–67) and median KPS 70 (60–90) at enrollment. 4 patients were treated at the highest dose 171mg/kg, where there was a single DLT: Grade 3 AST & ALT. The most common grade 1–2 AEs possibly, probably or definitely related to drug were elevated AST, rash, and fatigue, each occurring in 3 patients. Median OS for 9 eligible/evaluable patients was 128 days (95% CI: 48–209) while PFS was 34 days (CI of mean 8.9). 3 patients are currently alive; 2 patients have survived >1 year. PK/PD data are being processed and will be presented. CONCLUSION This study confirms that BPM 31510 + vitamin K is safe and feasible in treatment-refractory HGG patients. Though this study demonstrates safety at 171mg/kg, the proposed dose for future studies in GB, based on additional pre-clinical and non-GB clinical data is 88mg/kg.

Advances in the therapy of high-grade glioma at relapse: pegylated liposomal doxorubicin

2002 ◽  
Vol 2 (5) ◽  
pp. 609-615 ◽  
Author(s):  
Peter Hau ◽  
Joerg Dietrich ◽  
Klaus Fabel ◽  
Ulrich Bogdahn
Keyword(s):  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
High Grade Glioma ◽  
High Grade

Temozolomide (TMZ) and lomustine (CCNU) in high grade glioma (HGG) patients: Phase I study

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 1577-1577
Author(s):  
S. Tafuto ◽  
R. Guarrasi ◽  
A. Tortoriello ◽  
F. Buzzi ◽  
P. Muto ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
High Grade Glioma ◽  
High Grade

Phase I study of aflibercept (VEGF Trap) and temozolomide in newly diagnosed, high-grade glioma.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 2043-2043
Author(s):  
J. F. De Groot ◽  
T. Cloughesy ◽  
F. S. Lieberman ◽  
S. M. Chang ◽  
A. M. P. Omuro ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
High Grade Glioma ◽  
High Grade ◽  
Newly Diagnosed ◽  
Vegf Trap

A phase I study of convection-enhanced delivery of nanoliposomal irinotecan using real-time imaging in patients with recurrent high grade glioma.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. TPS2081-TPS2081
Author(s):  
Nicholas A. Butowski ◽  
Seunggu Han ◽  
Jennie Webster Taylor ◽  
Manish K. Aghi ◽  
Michael Prados ◽  
...  
Keyword(s):  
Phase I ◽  
Real Time ◽  
Phase I Study ◽  
High Grade Glioma ◽  
High Grade ◽  
Convection Enhanced Delivery ◽  
Real Time Imaging ◽  
Nanoliposomal Irinotecan

Phase I study of BPM31510 and vitamin K in patients with high grade glioma recurrent after a bevacizumab-containing regimen.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2543-2543
Author(s):  
Seema Nagpal ◽  
Reena Parada Thomas ◽  
Sophie Bertrand ◽  
Hari Priya Yerraballa ◽  
Michael Iv ◽  
...  
Keyword(s):  
Phase I ◽  
Vitamin K ◽  
Phase I Study ◽  
High Grade Glioma ◽  
Clinical Development ◽  
High Grade ◽  
Open Label ◽  
Tumor Bed ◽  
Mitochondrial Superoxide ◽  
Open Label Phase

2543 Background: BPM31510 is an ubidecarenone-lipid conjugate nanodispersion in clinical development for advanced malignancies, including high grade glioma (HGG). BPM31510’s anti-cancer effect is mediated by induction of mitochondrial superoxide and activation of cell death in glioblastoma models. Herein, we present preliminary pharmaco-kinetic and dynamic data, and survival from a phase I study of BPM31510 + Vitamin K in HGG with progression after bevacizumab (BEV). Methods: This was an open-label phase I study of BPM31510 continuous infusion with Vitamin K (10mg IM qweek) using a mTPI design, starting at 110mg/kg 2X/week, allowing 2 dose escalations & 1 de-escalation. Patients had received ChemoRT and were in recurrence after BEV. Results: Of 12 patients treated with BPM31510, 9 completed the 28-day DLT period. 2 patients came off study for progressive disease; 1 patient after asymptomatic hemorrhage into tumor bed (G1). 10 patients had primary GB, 2 had AA. Median age was 54.5yo (27-67) and KPS 70 (60-90). On Day 1 of BPM31510, a dose dependent increase in Cmax was observed; Tmax values were similar for all doses. AUC was linear with dose escalation. For all doses, Day 4 Cmax values were higher compared to Day 1. In contrast there was variable decrease in Tmax (table). Of evaluable patients, 4 patients received the highest dose 171mg/kg, where a single patient experienced DLT: G3 AST & ALT. The most common grade 1/2 AEs were elevated AST, rash, and fatigue, each occurring in 4 patients. The mOS for 9 eligible/evaluable patients was 128 days (95% CI: 48-209) while PFS was 34 days (95% CI of mean 8.9). Two patients are currently alive >12 months. Conclusions: BPM31510 + vitamin K demonstrated a safe profile to maximum dose of 171mg/kg twice/week with potential therapeutic utility in treatment-refractory HGG patients. Multi-omic molecular profiles characterizing AE and response to be reported from the study will be investigated for next phase of clinical development. Clinical trial information: NCT03020602 . [Table: see text]

scholarly journals A dose escalating phase I study of GLPG0187, a broad spectrum integrin receptor antagonist, in adult patients with progressive high-grade glioma and other advanced solid malignancies

2016 ◽  
Vol 34 (2) ◽  
pp. 184-192 ◽  
Author(s):  
Geert A. Cirkel ◽  
Bojana Milojkovic Kerklaan ◽  
Frédéric Vanhoutte ◽  
Annegret Van der Aa ◽  
Giocondo Lorenzon ◽  
...  
Keyword(s):  
Phase I ◽  
Receptor Antagonist ◽  
Broad Spectrum ◽  
Phase I Study ◽  
High Grade Glioma ◽  
Adult Patients ◽  
High Grade ◽  
Integrin Receptor ◽  
Solid Malignancies ◽  
Dose Escalating

Extended follow-up of outcome measures in multiple myeloma patients treated on a phase I study with bortezomib and pegylated liposomal doxorubicin

2006 ◽  
Vol 86 (3) ◽  
pp. 211-216 ◽  
Author(s):  
Suzanne E. Biehn ◽  
Dominic T. Moore ◽  
Peter M. Voorhees ◽  
Reynaldo A. Garcia ◽  
Mary Jo Lehman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase I ◽  
Outcome Measures ◽  
Phase I Study ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin
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