Phase I trial of alisertib with concurrent fractionated stereotactic re-irradiation for recurrent high grade gliomas.
Adult
Aged
Azepines
/ therapeutic use
Brain Neoplasms
/ drug therapy
Chemoradiotherapy
Cohort Studies
Female
Glioma
/ drug therapy
Humans
Male
Middle Aged
Neoplasm Recurrence, Local
/ pathology
Protein Kinase Inhibitors
/ therapeutic use
Pyrimidines
/ therapeutic use
Radiosurgery
/ methods
Re-Irradiation
Treatment Outcome
Alisertib
Anaplastic astrocytoma
Glioblastoma
Phase I clinical trial
Recurrence
Stereotactic radiation therapy
Journal
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
ISSN: 1879-0887
Titre abrégé: Radiother Oncol
Pays: Ireland
ID NLM: 8407192
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
09
10
2018
revised:
17
12
2018
accepted:
17
12
2018
entrez:
4
3
2019
pubmed:
4
3
2019
medline:
29
1
2020
Statut:
ppublish
Résumé
We conducted a phase I trial of alisertib, an oral aurora kinase inhibitor, with fractionated stereotactic re-irradiation therapy (FSRT) for patients with recurrent high grade glioma (HGG). Adult patients with recurrent HGG were enrolled from Feb 2015 to Feb 2017. Patients were treated with concurrent FSRT and alisertib followed by maintenance alisertib. Concurrent alisertib dose was escalated from 20 mg to 50 mg twice daily (BID). 17 patients were enrolled. Median follow-up was 11 months. Median FSRT dose was 35 Gy. There were 6, 6, 3, and 2 patients enrolled in 20 mg, 30 mg, 40 mg, and 50 mg cohort, respectively. Only one DLT was observed. One patient in the 20 mg cohort had severe headache (Grade 3) resolved with steroids. There was no non-hematological grade 3 or higher toxicity. There were two Grade 4 late toxicities (one with grade 4 neutropenia and leukopenia, one with pulmonary embolism). One patient developed radiation necrosis (Grade 3). Sixteen patients finished concurrent treatment and received maintenance therapy (median cycles was 3, range 1-9). OS for all cohorts at 6 months was 88.2% with median survival time of 11.1 months. PFS at 6 months was 35.3% with median time to progression of 4.9 months. The trial stopped early due to closure of alisertib program with only 2 of 3 planned patients enrolled in the 50 mg cohort. Re-irradiation with FSRT combined with alisertib is safe and well tolerated for HGG with doses up to 40 mg BID. Although no DLT observed in the 50 mg cohort, this cohort was not fully enrolled and MTD was not reached. Clinical outcomes appear comparable to historical results. (NCT02186509).
Sections du résumé
BACKGROUND AND PURPOSE
We conducted a phase I trial of alisertib, an oral aurora kinase inhibitor, with fractionated stereotactic re-irradiation therapy (FSRT) for patients with recurrent high grade glioma (HGG).
MATERIALS AND METHODS
Adult patients with recurrent HGG were enrolled from Feb 2015 to Feb 2017. Patients were treated with concurrent FSRT and alisertib followed by maintenance alisertib. Concurrent alisertib dose was escalated from 20 mg to 50 mg twice daily (BID).
RESULTS
17 patients were enrolled. Median follow-up was 11 months. Median FSRT dose was 35 Gy. There were 6, 6, 3, and 2 patients enrolled in 20 mg, 30 mg, 40 mg, and 50 mg cohort, respectively. Only one DLT was observed. One patient in the 20 mg cohort had severe headache (Grade 3) resolved with steroids. There was no non-hematological grade 3 or higher toxicity. There were two Grade 4 late toxicities (one with grade 4 neutropenia and leukopenia, one with pulmonary embolism). One patient developed radiation necrosis (Grade 3). Sixteen patients finished concurrent treatment and received maintenance therapy (median cycles was 3, range 1-9). OS for all cohorts at 6 months was 88.2% with median survival time of 11.1 months. PFS at 6 months was 35.3% with median time to progression of 4.9 months. The trial stopped early due to closure of alisertib program with only 2 of 3 planned patients enrolled in the 50 mg cohort.
CONCLUSION
Re-irradiation with FSRT combined with alisertib is safe and well tolerated for HGG with doses up to 40 mg BID. Although no DLT observed in the 50 mg cohort, this cohort was not fully enrolled and MTD was not reached. Clinical outcomes appear comparable to historical results. (NCT02186509).
Identifiants
pubmed: 30825962
pii: S0167-8140(18)33658-2
doi: 10.1016/j.radonc.2018.12.019
pii:
doi:
Substances chimiques
Azepines
0
MLN 8237
0
Protein Kinase Inhibitors
0
Pyrimidines
0
Banques de données
ClinicalTrials.gov
['NCT02186509']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
135-141Informations de copyright
Copyright © 2018 Elsevier B.V. All rights reserved.