A phase II prospective study of selumetinib in children with recurrent or refractory low-grade glioma (LGG): A Pediatric Brain Tumor Consortium (PBTC) study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10504-10504 ◽  
Author(s):  
Jason R. Fangusaro ◽  
Arzu Onar-Thomas ◽  
Tina Young-Poussaint ◽  
Shengjie Wu ◽  
Azra H Ligon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Pediatric Brain Tumor ◽  
Braf V600e Mutation ◽  
Low Grade Glioma ◽  
Braf V600e ◽  
Low Grade ◽  
Optic Pathway ◽  
Grade 3 ◽  
Molecular Aberrations

10504 Background: A greater understanding of the Ras-MAP kinase-signaling pathway in pediatric low-grade glioma (LGG) paired with the availability of potent selective inhibitors has enhanced the ability to target this pathway with therapeutic intent. Methods: The PBTC conducted a multi-institutional phase II study (NCT01089101) evaluating selumetinib (AZD6244, ARRY-142886), a MEK I/II inhibitor, in children with recurrent/refractory LGG assigned to 6 strata and treated at 25 mg/m2/dose PO BID for up to two years. Here we present the data from three of these strata. The remaining strata are still accruing patients. Results: Stratum I included children with non-NF-1 and non-optic pathway recurrent/refractory pilocytic astrocytoma (PA) harboring BRAF aberrations (BRAF V600e mutation or the BRAF-KIAA 1549 fusion). Eight of 25 (32%) patients achieved a partial response (PR) with 2-year PFS of 66+/-11%. Two of 7 (29%) patient tumors with a BRAF V600e mutation and 6/18 (33%) with a BRAF KIAA-1549 fusion had a PR. Stratum 3 enrolled NF-1-associated LGG. Tissue for tumor BRAF evaluation was not required for eligibility. Ten of 25 (40%) achieved PR with a 2-year PFS of 96+/-4%. Only one patient progressed while on treatment. Stratum 4 included children with non-NF-1 optic pathway/hypothalamic LGG. Tissue for tumor BRAF evaluation was not required for eligibility. Two of 16 (12.5%) had a PR with a 2-year PFS of 65+/-13%. The BRAF aberration status of the responders in strata 3 and 4 is mostly unknown. All responses were confirmed centrally and seven patients remain on treatment. The most common toxicities were grade 1/2 CPK elevation, diarrhea, hypoalbuminemia, elevated AST and rash. Rare grade 3/4 toxicities included elevated CPK, rash, neutropenia, emesis and paronychia. Conclusions: Selumetinib was effective in treating children with recurrent/refractory LGG, including those with NF-1 associated LGG and PA harboring BRAF V600e mutation or BRAF-KIAA 1549 fusion. Larger prospective studies are necessary to determine the future, specific role of this agent in treating children with LGG harboring specific molecular aberrations. Clinical trial information: NCT01089101.

scholarly journals LGG-08. A PHASE II PROSPECTIVE STUDY OF SELUMETINIB IN CHILDREN WITH RECURRENT OR REFRACTORY LOW-GRADE GLIOMA (LGG): A PEDIATRIC BRAIN TUMOR CONSORTIUM (PBTC) STUDY

2017 ◽  
Vol 19 (suppl_4) ◽  
pp. iv34-iv35 ◽  
Author(s):  
Jason Fangusaro ◽  
Arzu Onar-Thomas ◽  
Tina Y Poussaint ◽  
Shengjie Wu ◽  
Azra H Ligon ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Prospective Study ◽  
Phase Ii ◽  
Pediatric Brain Tumor ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Pediatric Brain

scholarly journals A phase II trial of selumetinib in children with recurrent optic pathway and hypothalamic low-grade glioma without NF1: a Pediatric Brain Tumor Consortium study

2021 ◽  
Author(s):  
Jason Fangusaro ◽  
Arzu Onar-Thomas ◽  
Tina Young Poussaint ◽  
Shengjie Wu ◽  
Azra H Ligon ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Visual Fields ◽  
Pediatric Brain Tumor ◽  
Progression Free Survival ◽  
Neurofibromatosis Type ◽  
Low Grade ◽  
Optic Pathway ◽  
Pediatric Brain

Abstract Background Pediatric low-grade gliomas (pLGGs) are the most common childhood brain tumor. Progression-free survival (PFS) is much lower than overall survival, emphasizing the need for alternative treatments. Sporadic (without neurofibromatosis type 1) optic pathway and hypothalamic gliomas (OPHGs) are often multiply recurrent and cause significant visual deficits. Recently, there has been a prioritization of functional outcomes. Methods We present results from children with recurrent/progressive OPHGs treated on a PBTC (Pediatric Brain Tumor Consortium) phase II trial evaluating efficacy of selumetinib (AZD6244, ARRY-142886) a MEK-1/2 inhibitor. Stratum 4 of PBTC-029 included patients with sporadic recurrent/progressive OPHGs treated with selumetinib at the recommended phase II dose (25mg/m2/dose BID) for a maximum of 26 courses. Results Twenty-five eligible and evaluable patients were enrolled with a median of 4 (1-11) previous therapies. Six of 25 (24%) had partial response, 14/25 (56%) had stable disease, and 5 (20%) had progressive disease while on treatment. The median treatment courses were 26 (2-26); 14/25 patients completed all 26 courses. Two-year PFS was 78 ± 8.5%. Nineteen of 25 patients were evaluable for visual acuity which improved in 4/19 patients (21%), was stable in 13/19 (68%), and worsened in 2/19 (11%). Five of 19 patients (26%) had improved visual fields and 14/19 (74%) were stable. The most common toxicities were grade 1/2 CPK elevation, anemia, diarrhea, headache, nausea/emesis, fatigue, AST and ALT increase, hypoalbuminemia, and rash. Conclusions Selumetinib was tolerable and led to responses and prolonged disease stability in children with recurrent/progressive OPHGs based upon radiographic response, PFS, and visual outcomes.

Phase II Trial of Temozolomide in Patients With Progressive Low-Grade Glioma

2003 ◽  
Vol 21 (4) ◽  
pp. 646-651 ◽  
Author(s):  
Jennifer A. Quinn ◽  
David A. Reardon ◽  
Allan H. Friedman ◽  
Jeremy N. Rich ◽  
John H. Sampson ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Malignant Gliomas ◽  
Progression Free Survival ◽  
Chemical Conversion ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Grade 3 ◽  
Experienced Grade

Purpose: Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studies have confirmed activity of Temodar in the treatment of progressive and newly diagnosed malignant gliomas. We have extended these results, and now we report results of a phase II trial of Temodar for patients with progressive, low-grade glioma. Patients and Methods: Temodar was administered orally once a day for five consecutive days (in a fasting state) at a starting dose of 200 mg/m2/d. Treatment cycles were repeated every 28 days following the first daily dose of Temodar. Response criteria used a combination of magnetic resonance imaging and physical examination to evaluate activity. Results: Forty-six patients with low-grade glioma have been treated to date. The objective response rate was 61% (24% complete response and 37% partial response), with an additional 35% of patients having stable disease. Median progression-free survival (PFS) was 22 months (95% confidence interval [CI], 15 to ∞ months) with a 6-month PFS of 98% (95% CI, 94% to 100%) and a 12-month PFS of 76% (95% CI, 63% to 92%). Toxicity observed during the study was limited to only six patients. Three patients experienced grade 3 neutropenia, with a duration greater than 3 weeks in one patient, and two patients experienced grade 3 thrombocytopenia. One patient experienced ≥ grade 4 toxicity, with intracerebral hemorrhage, neutropenia, thrombocytopenia, sepsis, and death. Conclusion:Initial results indicate that Temodar may be active in the treatment of low-grade glioma, and thus, further evaluation of this agent in the treatment of these tumors is warranted.

Diencephalic pediatric low-grade glioma harboring the BRAF V600E mutation presenting with various morphologies in sequential biopsy specimens

2017 ◽  
Vol 34 (4) ◽  
pp. 165-171 ◽  
Author(s):  
Yukitomo Ishi ◽  
Kanako C. Hatanaka ◽  
Shigeru Yamaguchi ◽  
Hiromi Fujita ◽  
Hiroaki Motegi ◽  
...  
Keyword(s):  
Braf V600e Mutation ◽  
Low Grade Glioma ◽  
Braf V600e ◽  
Low Grade ◽  
Biopsy Specimens

scholarly journals LTBK-01. UPDATES ON THE PHASE II AND RE-TREATMENT STUDY OF AZD6244 (SELUMETINIB) FOR CHILDREN WITH RECURRENT OR REFRACTORY PEDIATRIC LOW GRADE GLIOMA: A PEDIATRIC BRAIN TUMOR CONSORTIUM (PBTC) STUDY

2018 ◽  
Vol 20 (suppl_2) ◽  
pp. i214-i214
Author(s):  
Jason R Fangusaro ◽  
Arzu Onar-Thomas ◽  
Tina Young Poussaint ◽  
Shengjie Wu ◽  
Azra H Ligon ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Phase Ii ◽  
Pediatric Brain Tumor ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Pediatric Brain

scholarly journals LGG-07. LOW-GRADE GLIOMA COMBINATION CHEMOTHERAPY MAY BE EFFECTIVE IN BRAF V600E CODON-MUTATED OPTIC PATHWAY GANGLIOGLIOMAS

2017 ◽  
Vol 19 (suppl_4) ◽  
pp. iv34-iv34
Author(s):  
Jeffrey Murray ◽  
David Donahue ◽  
Hayden Head ◽  
Mandy Mansell ◽  
Linda Margraf
Keyword(s):  
Combination Chemotherapy ◽  
Low Grade Glioma ◽  
Braf V600e ◽  
Low Grade ◽  
Optic Pathway

Therapie des BRAF-mutierten NSCLC

2018 ◽  
Vol 09 (05) ◽  
pp. 239-239
Author(s):  
Dr. Susanne Krome
Keyword(s):  
Phase Ii ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Alk Rearrangement

BRAF-mutierte nicht kleinzellige Bronchialkarzinome (NSCLC) sind besonders aggressiv. Gezielte Antikörpertherapien verbesserten die Behandlungsergebnisse. Bei einem ALK-Rearrangement ging eine lange progressionsfreie Zeit nicht zu Lasten der Post-Progressionsphase. Die Sekundäranalyse einer nicht randomisierten Phase-II-Studie zeigt dies nun auch für Patienten mit einer BRAF-V600E-Mutation.

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