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A phase II single-arm study of irinotecan in combination with temozolomide (TEMIRI) in children with newly diagnosed high grade glioma: a joint ITCC and SIOPE-brain tumour study

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Abstract

A multicenter, two stage phase II study, investigated irinotecan plus temozolomide in children with newly diagnosed high grade glioma. The primary endpoint was tumor response during a two-cycle treatment window, confirmed by external review committee. Patients received oral temozolomide 100 mg/(m2 day) (days 1–5) and intravenous irinotecan 10 mg/(m2 day) (days 1–5 and 8–12) for two 21-day cycles (three cycles for patients exhibiting objective tumor response). Standard treatment was then administered according to local investigator choice. In total 17 patients were enrolled and treated by local investigators. However, central pathology review found three patients did not have a diagnosis of high grade glioma and another four patients did not have evaluable disease according to independent central radiological review. The primary endpoint was based on the first ten evaluable patients as determined by the external review committee. Recruitment was stopped for futility after there were no complete or partial responses during the two-cycle treatment window in the first ten evaluable patients. Five patients had stable disease, and five progressed. Data for secondary endpoints including; time to tumor progression, time to treatment failure, and overall survival is reported. The safety profile of the treatment showed the combination was tolerable with two patients (11.8 %) having grade three nausea, and one (5.9 %) experiencing a grade four neutropenia, leading to permanent discontinuation from adjuvant treatment. Irinotecan plus temozolomide, although well tolerated did not improve outcome over historical controls in this setting.

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Acknowledgments

Thank you to all the patients and their families that participated in the study and to all investigators and their teams, and Dr Paul Hoban from Cancer Communications & Consultancy Ltd (medical writing services) funded by Pfizer.

Conflict of interest

  LC, AB, and AD are employees of Pfizer.

Funding

  The study was sponsored by Pfizer Oncology.

Author information

Authors and Affiliations

  1. Paediatric Oncology Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK

    Darren Hargrave

  2. Department of Paediatric and Adolescent Oncology, University Paris-Sud XI, Institut Gustave Roussy, Villejuif, France

    Birgit Geoerger & Jacques Grill

  3. Institut d’Hémato-Oncologie Pédiatrique, Centre Léon Bérard, Lyon, France

    Didier Frappaz

  4. Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany

    Torsten Pietsch

  5. Department of Radiology, St. Barnabas Medical Center, Livingston, USA

    Lyle Gesner

  6. Pfizer Inc., New York, USA

    Laura Cisar, Aurora Breazna & Andrew Dorman

  7. Servicios de Pediatría, Unidad Integrada Hospital Sant Joan de Déu-Clínic, Universidad de Barcelona, Barcelona, Spain

    Ofelia Cruz-Martinez

  8. Pathology Services, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain

    Jose Luis Fuster

  9. Centre Robert Debré, CHU Angers, Angers, France

    Xavier Rialland

  10. Groupe Hospitalier Pellegrin, Hôpital Pellegrin CHU Bordeaux, Bordeaux, France

    Céline Icher

  11. Centre Oscar-Lambret, Unité d’Oncologie Pédiatrique, Lille, France

    Pierre Leblond

  12. The Andrew Love Cancer Centre, Geelong Hospital, Deakin University, Geelong, Australia

    David Ashley

  13. Department of Paediatrics, University of Padua, Padua, Italy

    Giorgio Perilongo

  14. Department of Paediatric Hematology and Oncology, Leeds General Infirmary, Leeds, UK

    Martin Elliott

  15. Paediatric Oncology, Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, UK

    Martin English

  16. Department of Paediatrics, University Hospital of Aarhus at Skejby, Aarhus, Denmark

    Niels Clausen

  17. Paediatric Oncology Unit, Royal Marsden NHS Foundation Trust, Sutton, UK

    Darren Hargrave

Authors
  1. Darren Hargrave
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  2. Birgit Geoerger
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  3. Didier Frappaz
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  4. Torsten Pietsch
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  5. Lyle Gesner
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  7. Aurora Breazna
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  9. Ofelia Cruz-Martinez
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  10. Jose Luis Fuster
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  11. Xavier Rialland
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  12. Céline Icher
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  13. Pierre Leblond
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  14. David Ashley
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  15. Giorgio Perilongo
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  16. Martin Elliott
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  17. Martin English
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  18. Niels Clausen
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  19. Jacques Grill
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Corresponding author

Correspondence to Darren Hargrave.

Additional information

This study was conducted on the behalf of the European Innovative Therapies for Children with Cancer (ITCC) and the SIOPE-Brain tumour group.

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Hargrave, D., Geoerger, B., Frappaz, D. et al. A phase II single-arm study of irinotecan in combination with temozolomide (TEMIRI) in children with newly diagnosed high grade glioma: a joint ITCC and SIOPE-brain tumour study. J Neurooncol 113, 127–134 (2013). https://doi.org/10.1007/s11060-013-1098-2

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