gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

A Clinical Phase I Study of the Triple Angiokinase Inhibitor BIBF 1120 in Advanced Cancer Patients

Meeting Abstract

  • corresponding author presenting/speaker Klaus Mross - Klinik für Tumorbiologie, Freiburg, Deutschland
  • A. Frost - Klinik für Tumorbiologie, Freiburg
  • D. Gmehling - Klinik für Tumorbiologie, Freiburg
  • F. Bass - Klinik für Tumorbiologie, Freiburg
  • C. Unger - Klinik für Tumorbiologie, Freiburg
  • R. Strecker - MR Development and Application Center, Freiburg
  • J. Hennig - MR Development and Application Center, Freiburg
  • G. Deichsel - Boehringer Ingelheim Pharma GmbH&C. KG
  • M. Stefanic - Boehringer Ingelheim Pharma GmbH&C. KG
  • P. Stopfer - Boehringer Ingelheim Pharma GmbH&C. KG
  • L. de Rossi - Boehringer Ingelheim Pharma GmbH&C. KG

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocOP441

The electronic version of this article is the complete one and can be found online at:

Published: March 20, 2006

© 2006 Mross et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Background: BIBF 1120 is a potent, orally available triple angiokinase inhibitor (VEGFRs, PDGFRs, FGFRs) that suppresses tumour growth. This Phase I study was performed to evaluate the maximum tolerated dose of BIBF 1120 in advanced cancer patients.

Methods: Treatment courses consisted of 28 days administration of BIBF 1120 followed by 7 days off. The dose was first escalated with once daily dosing (QD) until dose limiting toxicity (DLT) was observed. In a second cohort, twice daily dosing (BID) was performed to further increase drug exposure. In all patients, additional treatment courses were allowed in the absence of progressive disease and persistent toxicity. PK profiles were obtained at beginning and at the end of the 1st course. Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE‑MRI) was performed at baseline, day 2/3, day 29/30 and after each further course.

Results: 61 patients (15 f, 46 m) were included, 52 completed the 1st treatment course and 9 patients were excluded due to unrelated adverse event (AE) or DLT. The dose of BIBF 1120 was escalated up to 450 mg QD and 300 mg BID, respectively. Predominant drug-related AEs (CTC-Grade < 2) were nausea, vomiting, diarrhoea and elevation of hepatic enzymes (LFT). LFT elevations were dose limiting (≥ CTCGrade3) in 2/5 patients at 300 mg QD, 2/3 patients at 450 mg QD and 2/5 patients at 300 mg BID. 33/61 patients were treated for more than 2 courses. The safety profile of BIBF 1120 did not deteriorate with repeated treatment courses. One patient showed a Complete Response at 200 mg QD and 2 patients showed a Partial Response at > 200 mg BID (RECIST criteria). In the DCE-MRI measurements, blood flow and permeability (Ktrans and/or IAUC60) in metastasis were reduced by > 40% compared to baseline in 24/42 evaluable patients. Exposure (AUC) to BIBF 1120 showed moderate to high variability and increased with dose. Maximum plasma concentrations were reached ~ 3 hours after drug intake. BIBF 1120 was extensively distributed out of the blood and showed a high clearance (absolute bioavailability unknown), mean terminal half-life was ~ 15 h. Steady state was reached latest at day 9.

Conclusion: BIBF1120 showed a favourable safety profile at doses up to 250 mg QD and 250 mg BID. AEs were mainly of gastrointestinal nature with mild to moderate intensity. Reversible LFT elevations constituted DLT. Based on these results, a dose of 250 mg QD or 250 mg BID when given continuously for 4 weeks are the MTD of BIBF 1120. In conclusion, these results provide evidence that patients with advanced cancers may have clinical benefit in terms of tumour size reduction and/or inhibition of tumour progression from treatment with BIBF 1120.