Phase I safety, pharmacokinetic, and biomarker study of BIBF 1120, an oral triple tyrosine kinase inhibitor in patients with advanced solid tumors

Molecular Cancer Therapeutics

Volumn 9, Issue 10, 2010, Pages 2825-2833

  Okamoto, Isamu ^a   Kaneda, Hiroyasu ^a   Satoh, Taroh ^a   Okamoto, Wataru ^a   Miyazaki, Masaki ^a   Morinaga, Ryotaro ^a   Ueda, Shinya ^a   Terashima, Masaaki ^a   Tsuya, Asuka ^a   Sarashina, Akiko ^b   Konishi, Koichi ^b   Arao, Tokuzo ^a   Nishio, Kazuto ^a   Kaiser, Rolf ^c   Nakagawa, Kazuhiko ^a  

^a KINKI UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^b NIPPON BOEHRINGER INGELHEIM CO LTD   (Japan)

^c BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

BIBF 1120; BIOLOGICAL MARKER; LIVER ENZYME; STEM CELL FACTOR RECEPTOR; VASCULOTROPIN RECEPTOR 2;

ABDOMINAL PAIN; ADULT; ANOREXIA; AREA UNDER THE CURVE; ARTICLE; CANCER SURVIVAL; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG ERUPTION; DRUG SAFETY; DRUG STRUCTURE; FATIGUE; FEMALE; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; HEMATOLOGIC DISEASE; HEMATOPOIETIC STEM CELL; HEMOPTYSIS; HUMAN; HYPERTENSION; MALE; NAUSEA; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEINURIA; SIDE EFFECT; SOLID TUMOR; UNSPECIFIED SIDE EFFECT; UPPER ABDOMINAL PAIN; VOMITING; WEIGHT;

ADMINISTRATION, ORAL; ANGIOGENESIS INHIBITORS; ANTINEOPLASTIC AGENTS; BIOLOGICAL MARKERS; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; INDOLES; MALE; NEOPLASMS;

EID: 77958038695     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-10-0379     Document Type: Article

References (24)

1. Taylor M, Rossler J, Geoerger B, et al. High levels of circulating VEGFR2+ bone marrow-derived progenitor cells correlate with metastatic disease in patients with pediatric solid malignancies. Clin Cancer Res 2009;15:4561-71.
2. Kerbel R, Folkman J. Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2002;2:727-39.
3. Morabito A, De Maio E, Di Maio M, Normanno N, Perrone F. Tyrosine kinase inhibitors of vascular endothelial growth factor receptors in clinical trials: current status and future directions. Oncologist 2006;11:753-64.
4. Bertolini F, Shaked Y, Mancuso P, Kerbel RS. The multifaceted circulating endothelial cell in cancer: towards marker and target identification. Nat Rev Cancer 2006;6:835-45.
5. Brown AP, Citrin DE, Camphausen KA. Clinical biomarkers of angiogenesis inhibition. Cancer Metastasis Rev 2008;27:415-34.
6. Agulnik M, Oza AM, Pond GR, Siu LL. Impact and perceptions of mandatory tumor biopsies for correlative studies in clinical trials of novel anticancer agents. J Clin Oncol 2006;24:4801-7.
7. Helft PR, Daugherty CK. Are we taking without giving in return? The ethics of research-related biopsies and the benefits of clinical trial participation. J Clin Oncol 2006;24:4793-5.
8. Drevs J, Siegert P, Medinger M, et al. Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors. J Clin Oncol 2007;25:3045-54.
9. Norden-Zfoni A, Desai J, Manola J, et al. Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic imatinib-resistant gastrointestinal stromal tumor. Clin Cancer Res 2007;13:2643-50.
10. Roth GJ, Heckel A, Colbatzky F, et al. Design, synthesis, and evaluation of indolinones as triple angiokinase inhibitors and the discovery of a highly specific 6-methoxycarbonyl-substituted indolinone (BIBF 1120). J Med Chem 2009;52:4466-80.
11. Hilberg F, Roth GJ, Krssak M, et al. BIBF1120: triple angiokinase inhibitor with sustained receptor blockade and good anti-tumor efficacy. Cancer Res 2008;68:4774-82.
12. Mross K, Stefanic M, Gmehling D, et al. Phase I study of the angiogenesis inhibitor BIBF 1120 in patients with advanced solid tumors. Clin Cancer Res 2010;16:311-9.
13. du Bois A, Huober J, Stopfer P, et al. A phase I open-label dose-escalation study of oral BIBF 1120 combined with standard paclitaxel and carboplatin in patients with advanced gynecological malignancies. Ann Oncol 2010;21:370-5.
14. Ledermann JA, Rustin GJ, Hackshaw A, et al. A randomized phase II placebo-controlled trial using maintenance therapy to evaluate the vascular targeting agent BIBF 1120 following treatment of relapsed ovarian cancer (OC). J Clin Oncol 2009;27:15s (abstr 5501).
15. von Pawel J, Kaiser R, Eschbach C, et al. Efficacy, safety and pharmacokinetic (PK) results of a phase II study with the triple angiokinase inhibitor BIBF 1120 in patients suffering from advanced non small cell lung cancer (NSCLC). J Thorac Oncol 2008;3:S61.
16. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205-16.
17. Faivre S, Djelloul S, Raymond E. New paradigms in anticancer therapy: targeting multiple signaling pathways with kinase inhibitors. Semin Oncol 2006;33:407-20.
18. Beaudry P, Force J, Naumov GN, et al. Differential effects of vascular endothelial growth factor receptor-2 inhibitor ZD6474 on circulating endothelial progenitors and mature circulating endothelial cells: implications for use as a surrogate marker of antiangiogenic activity. Clin Cancer Res 2005;11:3514-22.
19. Beerepoot LV, Mehra N, Vermaat JS, Zonnenberg BA, Gebbink MF, Voest EE. Increased levels of viable circulating endothelial cells are an indicator of progressive disease in cancer patients. Ann Oncol 2004;15:139-45.
20. Mancuso P, Burlini A, Pruneri G, Goldhirsch A, Martinelli G, Bertolini F. Resting and activated endothelial cells are increased in the peripheral blood of cancer patients. Blood 2001;97:3658-61.
21. Stamper IJ, Byrne HM, Owen MR, Maini PK. Modelling the role of angiogenesis and vasculogenesis in solid tumour growth. Bull Math Biol 2007;69:2737-72.
22. Summer R, Kotton DN, Sun X, Fitzsimmons K, Fine A. Translational physiology: origin and phenotype of lung side population cells. Am J Physiol Lung Cell Mol Physiol 2004;287:L477-83.
23. Blair A, Sutherland HJ. Primitive acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo lack surface expression of c-kit (CD117). Exp Hematol 2000;28:660-71.
24. Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker PH, Verfaillie CM. Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest 2002;109:337-46.