scholarly journals ACTR-67. A PHASE I STUDY OF CONVECTION-ENHANCED DELIVERY OF LIPOSOMAL-IRINOTECAN (ONIVYDE) USING REAL-TIME IMAGING WITH GADOLINIUM IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMAS: RESULTS THUS FAR

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi26-vi27 ◽  
Author(s):  
Karishma Kumar ◽  
Susan Chang ◽  
Nancy Ann Oberheim-Bush ◽  
Jennifer Clarke ◽  
Jennie Taylor ◽  
...  
Keyword(s):  
Phase I ◽  
Real Time ◽  
Phase I Study ◽  
High Grade ◽  
Convection Enhanced Delivery ◽  
Real Time Imaging ◽  
High Grade Gliomas ◽  
Liposomal Irinotecan

scholarly journals A PHASE I STUDY OF CONVECTION-ENHANCED DELIVERY OF LIPOSOMAL-IRINOTECAN USING REAL-TIME IMAGING WITH GADOLINIUM IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMA

2014 ◽  
Vol 16 (suppl 3) ◽  
pp. iii13-iii13 ◽  
Author(s):  
N. Butowski ◽  
K. Bankiewicz ◽  
A. Kells ◽  
A. Martin ◽  
M. Berger ◽  
...  
Keyword(s):  
Phase I ◽  
Real Time ◽  
Phase I Study ◽  
High Grade Glioma ◽  
High Grade ◽  
Convection Enhanced Delivery ◽  
Real Time Imaging ◽  
Liposomal Irinotecan

scholarly journals ACTR-33. A PHASE I STUDY OF CONVECTION-ENHANCED DELIVERY OF LIPOSOMAL-IRINOTECAN USING REAL-TIME IMAGING WITH GADOLINIUM IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMA

2016 ◽  
Vol 18 (suppl_6) ◽  
pp. vi9-vi9
Author(s):  
Seunggu Han ◽  
Jennie Taylor ◽  
Manish Aghi ◽  
Susan Chang ◽  
Jennifer Clarke ◽  
...  
Keyword(s):  
Phase I ◽  
Real Time ◽  
Phase I Study ◽  
High Grade Glioma ◽  
High Grade ◽  
Convection Enhanced Delivery ◽  
Real Time Imaging ◽  
Liposomal Irinotecan

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

scholarly journals SCIDOT-02. A PHASE I STUDY OF CONVECTION-ENHANCED DELIVERY OF LIPOSOMAL-IRINOTECAN (ONIVYDE) USING REAL-TIME IMAGING WITH GADOLINIUM IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMAS: RESULTS THUS FAR

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi272-vi272
Author(s):  
Karishma Kumar ◽  
Nicholas Butowski ◽  
Manish Aghi ◽  
Krystof Bankiewicz ◽  
John Bringas ◽  
...  
Keyword(s):  
Real Time ◽  
Drug Distribution ◽  
Volume Of Distribution ◽  
High Grade ◽  
Convection Enhanced Delivery ◽  
Post Infusion ◽  
Fluid Convection ◽  
Nanoliposomal Irinotecan ◽  
High Grade Gliomas ◽  
Liposomal Irinotecan

Abstract BACKGROUND Chemotherapy for high grade gliomas (HGG) is limited by the blood-brain-barrier (BBB). Convection enhanced delivery (CED) improves chemotherapy delivery by utilizing fluid convection obviating the challenges of crossing the BBB while minimizing systemic toxicity. CED of nanoliposomal-irinotecan (Onivyde) showed to be a superior delivery route for anti-tumor activity in animal models. An advance of this trial is the development and use of real time CED, which utilizes MRI to visualize the CED process with the aid of co-convected contrast agents, monitoring delivery into the brain and affording for corrective action. METHODS This is a 3 + 3 single dose escalation trial with 2 cohorts: 20mg/ml and 40mg/ml. Onivyde and GAD were co-infused via the same catheters in a one-time delivery. The total dose was personalized based on the patient’s tumor volume, and ranged from 20–680 mg of Onivyde, given via up to 4 catheters. Tumor diameters were allowed to be 1 – 4 cm, with injection volumes ranging from 2 – 17 mL of infusate. RESULTS 13 patients have been treated on this protocol, all in under 5 hours. There were 9 GBs, 1 gliosarcoma, 2 AAs, and 1 oligoastrocytoma. Utilizing imaging software, we correlated pre-infusion modeling of the drug distribution with post-infusion imaging. A number of technical challenges were overcome by real time monitoring; the total volume of distribution (Vd), and the Vd to volume infused (Vi) ratio for each infusion was ~2. Of all patients, the only notable AE was encephalopathy, which was resolved. CONCLUSIONS Image-guided distribution allows for safe real-time placement and adjustment of CED cannula of Onivyde into patient’s brains. Such methods allow for maximum tumor coverage and warrant further studies with repeat dosing.

scholarly journals EPCT-19. A PHASE I STUDY OF RIBOCICLIB AND EVEROLIMUS FOLLOWING RADIATION THERAPY IN CHILDREN WITH NEWLY DIAGNOSED NON-BIOPSIED DIFFUSE PONTINE GLIOMAS (DIPG) AND RB+ BIOPSIED DIPG AND HIGH GRADE GLIOMAS (HGG)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii307-iii307
Author(s):  
Mariko DeWire ◽  
James Leach ◽  
Christine Fuller ◽  
Peter de Blank ◽  
Trent Hummel ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Single Agent ◽  
Maximum Tolerated Dose ◽  
Pharmacokinetic Studies ◽  
High Grade ◽  
Newly Diagnosed ◽  
High Grade Gliomas ◽  
Grade 3 ◽  
Expansion Cohort

Abstract Genomic aberrations in the cell cycle and mTOR pathways have been reported in diffuse pontine gliomas (DIPG) and high-grade gliomas (HGG). Dual inhibition of CDK4/6 (ribociclib) and mTOR (everolimus) has strong biologic rationale, non-overlapping single-agent toxicities, and adult clinical experience. The maximum tolerated dose (MTD) and/or recommended phase two dose (RP2D) of ribociclib and everolimus administered during maintenance therapy following radiotherapy was determined in the phase I study as a rolling 6 design. Ribociclib and everolimus were administered once daily for 21 days and 28 days, respectively starting two-four weeks post completion of radiotherapy. All HGG patients and any DIPG patient who had undergone biopsy were screened for RB protein by immunohistochemistry. Eighteen eligible patients enrolled (median age 8 years; range: 2–18). Six patients enrolled at dose levels 1,2, and 3 without dose limiting toxicities (DLT). Currently, five patients are enrolled at dose level 3 expansion cohort. The median number of cycles are 4.5 (range: 1–20+). Among the expansion cohort, one dose limiting toxicity included a grade 3 infection and one patient required a dose reduction in course 3 due to grade 3 ALT and grade 4 hypokalemia. The most common grade 3/4 adverse events included neutropenia. Preliminary pharmacokinetic studies on 12 patients suggest an impact of ribociclib on everolimus pharmacokinetics. The MTD/RP2D of ribociclib and everolimus following radiotherapy in newly diagnosed DIPG and HGG is anticipated to be 170 mg/m2/day x 21 days and 1.5 mg/ m2/day every 28 days which is equivalent to the adult RP2D.

A phase I study of temozolomide and lapatinib combination in patients with recurrent high-grade gliomas

2013 ◽  
Vol 260 (6) ◽  
pp. 1469-1480 ◽  
Author(s):  
Vasilios Karavasilis ◽  
Vassiliki Kotoula ◽  
George Pentheroudakis ◽  
Despina Televantou ◽  
Sofia Lambaki ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
High Grade ◽  
High Grade Gliomas

scholarly journals AT-51 * PHASE I STUDY OF PANOBINOSTAT AND FRACTIONATED STEREOTACTIC RE-IRRADIATION THERAPY (FSRT) FOR RECURRENT HIGH GRADE GLIOMAS

2014 ◽  
Vol 16 (suppl 5) ◽  
pp. v19-v20
Author(s):  
W. Shi ◽  
Y. R. Lawrence ◽  
M. Werner-wasik ◽  
J. Evans ◽  
D. Andrews ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
High Grade ◽  
Irradiation Therapy ◽  
High Grade Gliomas

Sequential therapy with the selective T-type calcium channel blocker mibefradil and temozolomide in patients with recurrent high-grade gliomas: An Adult Brain Tumor Consortium phase I study (ABTC1101).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS2105-TPS2105 ◽  
Author(s):  
Matthias Holdhoff ◽  
Stuart A. Grossman ◽  
Jeffrey G. Supko ◽  
Xiaobu Ye ◽  
Joy D. Fisher ◽  
...  
Keyword(s):  
Phase I ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Phase I Study ◽  
Channel Blocker ◽  
Standard Dose ◽  
S Phase ◽  
Adult Brain ◽  
High Grade ◽  
High Grade Gliomas

TPS2105 Background: Despite recent advances in their treatment, high-grade gliomas (HGG) carry a dismal prognosis. Treatment options at recurrence are particularly limited and a re-challenge with temozolomide (TMZ) frequently appears as the most appropriate systemic treatment option in patients whose progression occurred off TMZ. This study investigates the sequential treatment of mibefradil (MIB), a selective Cav3 calcium channel blocker, and standard dose TMZ. Preclinical data showed that Cav3 inhibitors such as MIB can slow tumor growth without significant effect on normal tissues and can induce cell cycle arrest in cancer cells at the G1/S-phase checkpoint. We hypothesize that withdrawal of MIB could synchronize and release cells into S-phase, thereby potentiating the cytotoxic effect of TMZ. Methods: This trial is an open-label, multicenter phase I study, structured into a dose escalation phase to determine the maximum tolerated dose of MIB (MTD; Primary Objective) and an expansion cohort of 10 patients at the MTD level. Adults with recurrent HGG (WHO grade 3 or 4) who have previously received standard adjuvant therapy with radiation (RT) and TMZ (last dose ≥ 3 months prior to enrollment) and who have not received other cytotoxic therapy (except for carmustine wafers) are eligible. Patients receive oral MIB for 7 days on a 4 x/day (QID) schedule, followed by standard dose TMZ at 150-200 mg/m2 for 5 days each 28-day cycle. Dose finding uses a modified 3+3 design, starting at MIB 25 mg po QID (100 mg/day) with dose increases of 25 mg/dose per dose level. The target dose-limiting toxicity (DLT) rate is ≤ 33%. Secondary Objectives: (1) safety and adverse event analysis (incl. cardiac monitoring during cycle 1), (2) pharmacokinetic profile of MIB, (3) response assessment (RANO criteria), and (4) assessment of the potential effect of MIB on tumor DNA synthesis as determined by fluorothymidine positron emission tomography (FLT PET; extension cohort). Enrollment status as of January 2013: cohort 1 completed without DLT; cohort 2 enrolling at MIB 200 mg/day. Clinical trial information: NCT01480050.

A phase I trial of intravenous liposomal irinotecan in patients with recurrent high-grade gliomas.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 2029-2029
Author(s):  
Jennifer Leigh Clarke ◽  
Annette M Molinaro ◽  
Ashley A DeSilva ◽  
Jane E Rabbitt ◽  
Daryl C. Drummond ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
High Grade ◽  
High Grade Gliomas ◽  
Liposomal Irinotecan
Sign in / Sign up

Export Citation Format

Share Document