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Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma

  • Antonio Silvani
  • Irene De SimoneEmail author
  • Vittorio Fregoni
  • Elena Biagioli
  • Enrico Marchioni
  • Manuela Caroli
  • Andrea Salmaggi
  • Andrea Pace
  • Valter Torri
  • Paola Gaviani
  • Erica Quaquarini
  • Giorgia Simonetti
  • Eliana Rulli
  • Maurizio D’Incalci
  • the Italian Association of Neuro-Oncology
Clinical Study

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.

Keywords

Glioblastoma Ortataxel Recurrence Taxane 

Notes

Acknowledgements

Authors commemorate the colleague Irene Floriani of the Mario Negri Institute, who passed away on 12 January 2016 and who dedicated her life to the research. She has been deeply involved in the statistical design and coordination of this clinical trial. Authors remember the colleague Dr Gian Antonio Da Prada of ICS Maugeri of Pavia, who passed away on 15th December 2015. He spent his life in the research and treatment of cancer with fully dedication and contributed in the drawing up and enrollment for this trial. Presentation: This work has not been yet presented. List of participating institutions and coauthors: Members of the Italian association of neuro-oncology (AINO): Antonio Silvani (Fondazione Istituto Neurologico Carlo Besta - IRCCS - Milano), Andrea Salmaggi (Ospedale A. Manzoni—Lecco), Manuela Caroli (Fondazione Ca’ Granda Ospedale Maggiore Policlinico—IRCCS—Milano), Enrico Marchioni (Fondazione Istituto Neurologico Nazionale Casimiro Mondino—IRCCS—Pavia), Andrea Pace (Istituto Nazionale Tumori Regina Elena—Roma), Paola Gaviani (Fondazione Istituto Neurologico Carlo Besta—IRCCS—Milano). Fondazione Istituto Neurologico Carlo BestaIRCCSMilano: UOC Neurologia 2—Neuroncologia clinica: A. Silvani, P. Gaviani, G. Simonetti. IRFMN (Istituto Ricerche Farmacologiche Mario Negri): Laboratorio di Metodologia per la Ricerca Clinica: I. De Simone, E. Biagioli, E. Rulli, V. Torri, Davide Poli, Evelina Mariotti, Grazia Caramia, Angela Pesenti Gritti, Ilaria Pacchetti. Laboratorio Farmacologia antitumorale: M. D’Incalci, Massimo Zucchetti. Fondazione Salvatore MaugeriIRCCSPavia: S.C. Oncologia: V. Fregoni, E. Quaquarini, Annalisa Lanza. Servizio di diagnostica per immagini: Gianpaolo Basso. Fondazione Istituto Neurologico Nazionale Casimiro MondinoIRCCSPavia: U.O. Neuroncologia: E. Marchioni, Paola Bini, Giulia Berzero, Luca Diamanti. Fondazione Ca’Granda Ospedale Maggiore PoliclinicoIRCCSMilano: U.O.C. Neurochirurgia: M.Caroli, Andrea Di Cristofori, Andrea Manzoni, Giordano Lanfranchi. Ospedale A. ManzoniLecco: S.C. Oncologia: A. Salmaggi, Antonio Ardizzoia. Istituto Nazionale Tumori Regina ElenaRoma: UOSD Neuroncologia: A. Pace, Veronica Villani.

Funding

This study was supported by Spectrum Pharmaceuticals Inc that supplied the study drug to the participating centres, without any costs or expenses.

Compliance with ethical standards

Conflict of interest

The authors declare no potential conflicts of interest with regard to the research, authorship, and/or publication of this article.

Supplementary material

11060_2019_3116_MOESM1_ESM.doc (532 kb)
Supplementary material 1 (DOC 531 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Antonio Silvani
    • 1
  • Irene De Simone
    • 2
    Email author
  • Vittorio Fregoni
    • 3
  • Elena Biagioli
    • 2
  • Enrico Marchioni
    • 4
  • Manuela Caroli
    • 5
  • Andrea Salmaggi
    • 6
  • Andrea Pace
    • 7
  • Valter Torri
    • 2
  • Paola Gaviani
    • 1
  • Erica Quaquarini
    • 3
  • Giorgia Simonetti
    • 1
  • Eliana Rulli
    • 2
  • Maurizio D’Incalci
    • 2
  • the Italian Association of Neuro-Oncology
  1. 1.Fondazione Istituto Neurologico Carlo BestaIRCCSMilanItaly
  2. 2.Istituto di Ricerche Farmacologiche Mario NegriIRCCSMilanItaly
  3. 3.Fondazione Salvatore MaugeriIRCCSPaviaItaly
  4. 4.Fondazione Istituto Neurologico Nazionale Casimiro MondinoIRCCSPaviaItaly
  5. 5.Fondazione Ca’Granda Ospedale Maggiore PoliclinicoIRCCSMilanItaly
  6. 6.Ospedale A. ManzoniLeccoItaly
  7. 7.Istituto Nazionale Tumori Regina ElenaRomaItaly

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