Abstract

BACKGROUND AND PURPOSE: Glioblastoma (GBM) is the most aggressive and frequent subtype of all malignant gliomas. At the time of recurrence, therapeutic options are lacking. Ortataxel, a second-generation taxane was reported to be effective in pre-clinical and phase I clinical studies. The aim of this study was to evaluate a potential therapeutic activity of ortataxel in patients with GBM recurring after surgery and first line treatment.

METHODS: In this phase II study, according to a two stage design, adult patients with histologically confirmed GBM in recurrence after surgery or biopsy, standard radiotherapy and chemotherapy with temozolomide were considered eligible. Patients included were treated with ortataxel 75 mg/m2 i.v. every 3 weeks until disease progression. The primary objective of the study was to evaluate the activity of ortataxel in terms of progression free survival (PFS) at 6 months after the enrollment. PFS, overall survival at 9 months after the enrollment, objective response rate, compliance and safety were evaluated as secondary endpoints.

RESULTS: Between Nov 26, 2013 and Dec 12, 2015, 40 patients were recruited across six centres. The number of patients alive and free from progression at 6 months after the enrollment, observed in the first stage was four (11.4%), out of 35 patients included in the analysis, below the minimum number of events (7 out of 33) required to continue the study with the second stage The most important toxicities were neutropenia and hepatotoxicity that occurred in 13.2% of patients and leukopenia that occurred in 15.8% of patients.

CONCLUSION: Overall ortataxel treatment fail to demonstrate a significant activity in recurrent GBM patients. However in a limited number of patients the drug produced a benefit that lasted for a long time.

TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number NCT01989884.

Original languageEnglish
Pages (from-to)455-62
Number of pages8
JournalJournal of Neuro-Oncology
Volume142
Issue number3
DOIs
Publication statusPublished - May 6 2019

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Glioblastoma
temozolomide
Disease-Free Survival
IDN 5109
Recurrence
Leukopenia
Therapeutics
Neutropenia
Glioma
Compliance
Disease Progression
Radiotherapy
Biopsy
Safety
Drug Therapy
Survival

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Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma. / Italian Association of Neuro-Oncology.

In: Journal of Neuro-Oncology, Vol. 142, No. 3, 06.05.2019, p. 455-62.

Research output: Contribution to journalArticle

Italian Association of Neuro-Oncology. / Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma. In: Journal of Neuro-Oncology. 2019 ; Vol. 142, No. 3. pp. 455-62.
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abstract = "BACKGROUND AND PURPOSE: Glioblastoma (GBM) is the most aggressive and frequent subtype of all malignant gliomas. At the time of recurrence, therapeutic options are lacking. Ortataxel, a second-generation taxane was reported to be effective in pre-clinical and phase I clinical studies. The aim of this study was to evaluate a potential therapeutic activity of ortataxel in patients with GBM recurring after surgery and first line treatment.METHODS: In this phase II study, according to a two stage design, adult patients with histologically confirmed GBM in recurrence after surgery or biopsy, standard radiotherapy and chemotherapy with temozolomide were considered eligible. Patients included were treated with ortataxel 75 mg/m2 i.v. every 3 weeks until disease progression. The primary objective of the study was to evaluate the activity of ortataxel in terms of progression free survival (PFS) at 6 months after the enrollment. PFS, overall survival at 9 months after the enrollment, objective response rate, compliance and safety were evaluated as secondary endpoints.RESULTS: Between Nov 26, 2013 and Dec 12, 2015, 40 patients were recruited across six centres. The number of patients alive and free from progression at 6 months after the enrollment, observed in the first stage was four (11.4{\%}), out of 35 patients included in the analysis, below the minimum number of events (7 out of 33) required to continue the study with the second stage The most important toxicities were neutropenia and hepatotoxicity that occurred in 13.2{\%} of patients and leukopenia that occurred in 15.8{\%} of patients.CONCLUSION: Overall ortataxel treatment fail to demonstrate a significant activity in recurrent GBM patients. However in a limited number of patients the drug produced a benefit that lasted for a long time.TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number NCT01989884.",
author = "{Italian Association of Neuro-Oncology} and Antonio Silvani and {De Simone}, Irene and Vittorio Fregoni and Elena Biagioli and Enrico Marchioni and Manuela Caroli and Andrea Salmaggi and Andrea Pace and Valter Torri and Paola Gaviani and Erica Quaquarini and Giorgia Simonetti and Eliana Rulli and Maurizio D'Incalci",
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T1 - Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma

AU - Italian Association of Neuro-Oncology

AU - Silvani, Antonio

AU - De Simone, Irene

AU - Fregoni, Vittorio

AU - Biagioli, Elena

AU - Marchioni, Enrico

AU - Caroli, Manuela

AU - Salmaggi, Andrea

AU - Pace, Andrea

AU - Torri, Valter

AU - Gaviani, Paola

AU - Quaquarini, Erica

AU - Simonetti, Giorgia

AU - Rulli, Eliana

AU - D'Incalci, Maurizio

PY - 2019/5/6

Y1 - 2019/5/6

N2 - BACKGROUND AND PURPOSE: Glioblastoma (GBM) is the most aggressive and frequent subtype of all malignant gliomas. At the time of recurrence, therapeutic options are lacking. Ortataxel, a second-generation taxane was reported to be effective in pre-clinical and phase I clinical studies. The aim of this study was to evaluate a potential therapeutic activity of ortataxel in patients with GBM recurring after surgery and first line treatment.METHODS: In this phase II study, according to a two stage design, adult patients with histologically confirmed GBM in recurrence after surgery or biopsy, standard radiotherapy and chemotherapy with temozolomide were considered eligible. Patients included were treated with ortataxel 75 mg/m2 i.v. every 3 weeks until disease progression. The primary objective of the study was to evaluate the activity of ortataxel in terms of progression free survival (PFS) at 6 months after the enrollment. PFS, overall survival at 9 months after the enrollment, objective response rate, compliance and safety were evaluated as secondary endpoints.RESULTS: Between Nov 26, 2013 and Dec 12, 2015, 40 patients were recruited across six centres. The number of patients alive and free from progression at 6 months after the enrollment, observed in the first stage was four (11.4%), out of 35 patients included in the analysis, below the minimum number of events (7 out of 33) required to continue the study with the second stage The most important toxicities were neutropenia and hepatotoxicity that occurred in 13.2% of patients and leukopenia that occurred in 15.8% of patients.CONCLUSION: Overall ortataxel treatment fail to demonstrate a significant activity in recurrent GBM patients. However in a limited number of patients the drug produced a benefit that lasted for a long time.TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number NCT01989884.

AB - BACKGROUND AND PURPOSE: Glioblastoma (GBM) is the most aggressive and frequent subtype of all malignant gliomas. At the time of recurrence, therapeutic options are lacking. Ortataxel, a second-generation taxane was reported to be effective in pre-clinical and phase I clinical studies. The aim of this study was to evaluate a potential therapeutic activity of ortataxel in patients with GBM recurring after surgery and first line treatment.METHODS: In this phase II study, according to a two stage design, adult patients with histologically confirmed GBM in recurrence after surgery or biopsy, standard radiotherapy and chemotherapy with temozolomide were considered eligible. Patients included were treated with ortataxel 75 mg/m2 i.v. every 3 weeks until disease progression. The primary objective of the study was to evaluate the activity of ortataxel in terms of progression free survival (PFS) at 6 months after the enrollment. PFS, overall survival at 9 months after the enrollment, objective response rate, compliance and safety were evaluated as secondary endpoints.RESULTS: Between Nov 26, 2013 and Dec 12, 2015, 40 patients were recruited across six centres. The number of patients alive and free from progression at 6 months after the enrollment, observed in the first stage was four (11.4%), out of 35 patients included in the analysis, below the minimum number of events (7 out of 33) required to continue the study with the second stage The most important toxicities were neutropenia and hepatotoxicity that occurred in 13.2% of patients and leukopenia that occurred in 15.8% of patients.CONCLUSION: Overall ortataxel treatment fail to demonstrate a significant activity in recurrent GBM patients. However in a limited number of patients the drug produced a benefit that lasted for a long time.TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number NCT01989884.

U2 - 10.1007/s11060-019-03116-z

DO - 10.1007/s11060-019-03116-z

M3 - Article

VL - 142

SP - 455

EP - 462

JO - Journal of Neuro-Oncology

JF - Journal of Neuro-Oncology

SN - 0167-594X

IS - 3

ER -