346 First in Pediatrics Phase I Study of Crenolanib Besylate (CP-868, 596–26) Administered During and After Radiation Therapy (RT) in Newly-diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) and Recurrent High Grade Glioma, Including DIPG (HGG)

2012 ◽  
Vol 48 ◽  
pp. 105-106
Author(s):  
C. Wetmore ◽  
A. Broniscer ◽  
K.D. Wright ◽  
A. Pai-Panandiker ◽  
Z. Patay ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Phase I ◽  
Phase I Study ◽  
High Grade Glioma ◽  
Diffuse Intrinsic Pontine Glioma ◽  
High Grade ◽  
Newly Diagnosed ◽  
Pontine Glioma

scholarly journals EPCT-06. A PHASE I STUDY OF MULTI-TARGETED THERAPY IN NEWLY DIAGNOSED OR PROGRESSIVE DIFFUSE INTRINSIC PONTINE GLIOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii304-iii305
Author(s):  
Muhammad Baig ◽  
Jason Johnson ◽  
Sumit Gupta ◽  
Zsila Sadighi ◽  
Wafik Zaky ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Maintenance Therapy ◽  
Phase I ◽  
Phase I Study ◽  
Diffusion Tensor ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Newly Diagnosed ◽  
Pontine Glioma ◽  
Dose Limiting Toxicity

Abstract BACKGROUND Diffuse intrinsic pontine glioma (DIPG) constitutes 80% of pediatric brain stem tumors with a median survival of 12 months. The PI3K/AKT/mTOR pathway is a key oncogenic driver of this tumor. Targeting the chromatin dysregulation through HDAC inhibition, demonstrated benefit in vivo and vitro studies. We completed the first study as a multi-targeted therapy using SAHA and temsirolimus in pediatric DIPG. METHODS After receiving institutional IRB approval, we enrolled 6 patients on this phase I study using a 3 + 3 statistical design. Patients were divided into stratum 1 and stratum 2, based on newly diagnosed or relapsed DIPG respectively. Stratum I patients received radiation therapy concurrently with vorinostat, followed by maintenance therapy with vorinostat and temsirolimus for 10 cycles (28 day cycle), while in stratum II patients received vorinostat and temsirolimus for 12 cycles. Neuroimaging including diffusion tensor imaging were evaluated where feasible. RESULTS Three patients were enrolled in each of the stratum. One patient in stratum 1 completed therapy, 2 other demonstrated progressive disease (PD) after 4th and 1st cycle of maintenance therapy respectively. In stratum 2 all patients progressed 2 months after the start of therapy. However no dose-limiting toxicity (DLT) was noted. The patient in stratum 1 who completed therapy, remained free of PD 21 months after diagnosis with continued improvements in the volume of enhancing and T2 hyperintense disease. CONCLUSION Although no significant benefit was seen as compared to historical controls during this study, no dose limiting toxicity was noticed with this treatment.

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

Phase I study of erlotinib administered concurrently with and after irradiation (RT) in the treatment of children, adolescents, and young adults with newly diagnosed intracerebral high-grade glioma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9553-9553
Author(s):  
A. Broniscer ◽  
S. J. Baker ◽  
T. E. Merchant ◽  
F. H. Laningham ◽  
M. Kocak ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
High Grade Glioma ◽  
Maximum Tolerated Dose ◽  
Exclusion Criterion ◽  
Pharmacokinetic Studies ◽  
High Grade ◽  
Newly Diagnosed ◽  
High Grade Gliomas ◽  
Grade 3

9553 Background: High-grade gliomas are uncommon neoplasms in childhood that portend a poor prognosis. Because of the promising activity of erlotinib in adults with high-grade glioma, we conducted this Phase I study to determine the maximum tolerated dose and dose limiting toxicity (DLT) of erlotinib administered concurrently with and after RT. Methods: Patients between 3 and 25 years of age with newly diagnosed high-grade glioma received erlotinib continuously once daily during and after RT for a maximum of 52 weeks. Pharmacokinetic studies of erlotinib and its metabolite OSI-420, and genotyping were performed during course 1 in consenting patients. Use of enzyme-inducing anticonvulsants was an exclusion criterion. Dose escalation followed a typical Phase I design (dosage levels of 70, 90, and 120 mg/m2 per day). The DLT-evaluation period comprised the first 8 weeks of erlotinib. Results: Seventeen patients (median age 10.4 yrs; 10 males) were enrolled. Diagnoses consisted of glioblastoma (n=9), anaplastic astrocytoma (n=4), and other high-grade gliomas (n=4). Two of seven patients experienced reversible grade 3 hypokalemia / hypophosphatemia at the 70 mg/m2 level. Once electrolyte abnormalities were excluded as DLT, only one of seven patients at the 120 mg/m2 level has experienced grade 3 diarrhea so far. Pharmacokinetic studies were obtained in 14/17 patients. At the 70 mg/m2 dosage level, the median (range) erlotinib and OSI-420 Cmax and Tmax were 1,405 ng/ml (937–2,180) and 4.1 hr (2.2–8.2) and 158.5 ng/ml (45–203) and 4.1 hr (2.2–7.9), respectively. Three patients have received erlotinib for more than 1 year with disease stabilization. Six patients have already experienced disease progression. Conclusions: Erlotinib administered concurrently with RT on this schedule has been well tolerated. Preliminary pharmacokinetic results are comparable to those observed in adults. Rather than continue to escalate erlotinib dosages, we plan to complete this study and open a phase II study of erlotinib and RT for this same patient population. No significant financial relationships to disclose.

Intraarterial delivery of bevacizumab and cetuximab utilizing blood-brain barrier disruption in children with high-grade glioma and diffuse intrinsic pontine glioma: results of a phase I trial

2021 ◽  
pp. 1-9
Author(s):  
Heather J. McCrea ◽  
Jana Ivanidze ◽  
Ashley O’Connor ◽  
Eliza H. Hersh ◽  
John A. Boockvar ◽  
...  
Keyword(s):  
Phase I ◽  
Blood Brain Barrier ◽  
Stable Disease ◽  
Phase I Trial ◽  
Progressive Disease ◽  
High Grade Glioma ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Brain Barrier ◽  
High Grade ◽  
Pontine Glioma

OBJECTIVE Delivery of drugs intraarterially to brain tumors has been demonstrated in adults. In this study, the authors initiated a phase I trial of superselective intraarterial cerebral infusion (SIACI) of bevacizumab and cetuximab in pediatric patients with refractory high-grade glioma (diffuse intrinsic pontine glioma [DIPG] and glioblastoma) to determine the safety and efficacy in this population. METHODS SIACI was used to deliver mannitol (12.5 ml of 20% mannitol) to disrupt the blood-brain barrier (BBB), followed by bevacizumab (15 mg/kg) and cetuximab (200 mg/m2) to target VEGF and EGFR, respectively. Patients with brainstem tumors had a balloon inflated in the distal basilar artery during mannitol infusion. RESULTS Thirteen patients were treated (10 with DIPG and 3 with high-grade glioma). Toxicities included grade I epistaxis (2 patients) and grade I rash (2 patients). There were no dose-limiting toxicities. Of the 10 symptomatic patients, 6 exhibited subjective improvement; 92% showed decreased enhancement on day 1 posttreatment MRI. Of 10 patients who underwent MRI at 1 month, 5 had progressive disease and 5 had stable disease on FLAIR, whereas contrast-enhanced scans demonstrated progressive disease in 4 patients, stable disease in 2, partial response in 2, and complete response in 1. The mean overall survival for the 10 DIPG patients was 519 days (17.3 months), with a mean posttreatment survival of 214.8 days (7.2 months). CONCLUSIONS SIACI of bevacizumab and cetuximab was well tolerated in all 13 children. The authors’ results demonstrate safety of this method and warrant further study to determine efficacy. As molecular targets are clarified, novel means of bypassing the BBB, such as intraarterial therapy and convection-enhanced delivery, become more critical. Clinical trial registration no.: NCT01884740 (clinicaltrials.gov)

scholarly journals Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma

2014 ◽  
Vol 110 (11) ◽  
pp. 2655-2661 ◽  
Author(s):  
A F Hottinger ◽  
A B Aissa ◽  
V Espeli ◽  
D Squiban ◽  
N Dunkel ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Phase I ◽  
Phase I Study ◽  
High Grade Glioma ◽  
High Grade ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment
Sign in / Sign up

Export Citation Format

Share Document