Journal of Neuro-Oncology

, Volume 111, Issue 2, pp 205–212 | Cite as

Phase II open-label study of nintedanib in patients with recurrent glioblastoma multiforme

  • Aida Muhic
  • Hans Skovgaard Poulsen
  • Morten Sorensen
  • Kirsten Grunnet
  • Ulrik Lassen
Clinical Study


Nintedanib (BIBF 1120) is a small, orally available, triple angiokinase inhibitor in phase III development (various indications) that targets VEGFR 1–3, FGFR 1–3, and PDGFR-α/β. This open-label, uncontrolled, phase II study assessed the efficacy and safety of nintedanib in patients with recurrent glioblastoma multiforme (GBM) who had previously failed radiotherapy plus temozolomide as first-line therapy (STUPP), or the same regimen with subsequent bevacizumab-based therapy as second-line treatment (BEV). Patients with a performance status of 0–1, histologically proven GBM, and measurable disease (by RANO) were enrolled. Nintedanib was given orally at a dose of 200 mg twice daily (bid), with magnetic resonance imaging undertaken every 8 weeks. The primary endpoint was objective response rate. The study was stopped prematurely following a preplanned futility analysis after inclusion of 13 patients in the STUPP arm and 12 in the BEV arm. Best response was stable disease (SD) in three patients (12 %); all other patients progressed within the first four 28-day cycles. One patient in the BEV arm has had SD for 17+ months. Median progression-free survival was 1 month and median overall survival was 6 months. Nintedanib had an acceptable safety profile, with no CTCAE grade 3–4 adverse events. Common adverse events were CTCAE grade 1–2 fatigue, loss of appetite, diarrhea, and nausea. Single-agent nintedanib (200 mg bid) demonstrated limited, but clinically non-relevant antitumor activity in patients with recurrent GBM who had failed 1–2 prior lines of therapy.


Glioblastoma Nintedanib (BIBF 1120) Angiogenesis inhibitors Phase II clinical trial 



Medical writing support, funded by Boehringer Ingelheim, was provided by Duncan Campbell of GeoMed in the production of this manuscript. This investigator-initiated study was supported by a research grant from Boehringer Ingelheim, Germany, who also provided the study medication.

Conflicts of interest

No authors have conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Aida Muhic
    • 1
  • Hans Skovgaard Poulsen
    • 1
    • 2
  • Morten Sorensen
    • 1
  • Kirsten Grunnet
    • 1
    • 2
  • Ulrik Lassen
    • 1
  1. 1.Department of Oncology 5073, Section for Neuro-oncology and Phase I UnitCopenhagenDenmark
  2. 2.Department of Radiation BiologyCopenhagenDenmark

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