Effect of small angiokinase inhibitor nintedanib (BIBF 1120) on QT interval in patients with previously untreated, advanced renal cell cancer in an open-label, phase II study

Investigational New Drugs

Volumn 31, Issue 5, 2013, Pages 1283-1293

  Eisen, Tim ^a   Shparyk, Yaroslav ^b   Macleod, Nicholas ^c   Jones, Robert ^c   Wallenstein, Gudrun ^d   Temple, Graham ^e   Khder, Yasser ^f   Dallinger, Claudia ^d   Studeny, Matus ^g   Loembe, Arsene Bienvenu ^g   Bondarenko, Igor ^h  

^a St John s Innovation Centre   (United Kingdom)

^b Chemotherapy Department   (Ukraine)

^c CRUK Clinical Research Unit (CRU)   (United Kingdom)

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

^e BOEHRINGER INGELHEIM LTD   (United Kingdom)

^f BOEHRINGER INGELHEIM   (France)

^g BOEHRINGER INGELHEIM RCV GMBH AND CO KG   (Austria)

^h Dnipropetrovsk State Medical Academy   (Ukraine)

Author keywords

Angiogenesis inhibitor; BIBF 1120; Nintedanib; Phase II; QT interval; RCC; Renal cell carcinoma

Indexed keywords

NINTEDANIB;

ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; CARDIOVASCULAR DISEASE; DIARRHEA; DRUG FATALITY; DRUG SAFETY; DRUG TOLERABILITY; DYSPEPSIA; ECG ABNORMALITY; FEMALE; FIRST DEGREE ATRIOVENTRICULAR BLOCK; HEART RATE; HUMAN; HYPERNATREMIA; HYPONATREMIA; KIDNEY CARCINOMA; MAJOR CLINICAL STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; MULTICENTER STUDY (TOPIC); NAUSEA; OPEN STUDY; PHASE 2 CLINICAL TRIAL (TOPIC); PR INTERVAL; PRIORITY JOURNAL; QRS COMPLEX; QT INTERVAL; QT PROLONGATION; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECTUM HEMORRHAGE; SIDE EFFECT; SINGLE DRUG DOSE; T WAVE; TIME TO MAXIMUM PLASMA CONCENTRATION; UPPER ABDOMINAL PAIN; VOMITING; XEROSTOMIA;

AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; CARCINOMA, RENAL CELL; ELECTROCARDIOGRAPHY; FEMALE; HUMANS; INDOLES; KIDNEY NEOPLASMS; MALE; MIDDLE AGED; PROTEIN KINASE INHIBITORS;

EID: 84884814024     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-013-9962-7     Document Type: Article

References (40)

1. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335-2342
2. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542-2550
3. Bergers G, Hanahan D (2008) Modes of resistance to anti-Angiogenic therapy. Nat Rev Cancer 8:592-603
4. Folkman J (2006) Antiangiogenesis in cancer therapy-endostatin and its mechanisms of action. Exp Cell Res 312:594-607
5. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ (2008) BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res 68:4774-4782
6. Bousquet G, Alexandre J, Le TC, Goldwasser F, Faivre S, de Mont-Serrat H, Kaiser R, Misset JL, Raymond E (2011) Phase I study of BIBF 1120 with docetaxel and prednisone in metastatic chemo-naive hormone-refractory prostate cancer patients. Br J Cancer 105:1640-1645
7. Mross K, Stefanic M, Gmehling D, Frost A, Baas F, Unger C, Strecker R, Henning J, Gaschler-Markefski B, Stopfer P, de Rossi L, Kaiser R (2010) Phase I study of the angiogenesis inhibitor BIBF 1120 in patients with advanced solid tumors. Clin Cancer Res 16:311-319
8. Reck M, Kaiser R, Eschbach C, Stefanic M, Love J, Gatzemeier U, Stopfer P, von Pawel J (2011) A phase II double-blind study to investigate efficacy and safety of two doses of the triple angiokinase inhibitor BIBF 1120 in patients with relapsed advanced non-small-cell lung cancer. Ann Oncol 22:1374-1381
9. Ledermann JA, Hackshaw A, Kaye S, Jayson G, Gabra H, McNeish I, Earl H, Perren T, Gore M, Persic M, Adams M, James L, Temple G, Merger M, Rustin G (2011) Randomized phase II placebo-controlled trial of maintenance therapy using the oral triple angiokinase inhibitor BIBF 1120 after chemotherapy for relapsed ovarian cancer. J Clin Oncol 29:3798-3804
10. Haverkamp W, Breithardt G, Camm AJ, Janse MJ, Rosen MR, Antzelevitch C, Escande D, Franz M, Malik M, Moss A, Shah R (2000) The potential for QT prolongation and pro-Arrhythmia by non-Anti-Arrhythmic drugs: clinical and regulatory implications. Report on a Policy Conference of the European Society of Cardiology. Cardiovasc Res 47:219-233
11. Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH (2002) Timing of new black box warnings and withdrawals for prescription medications. JAMA 287:2215-2220
12. ICH Steering Committee (2012) The clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-Antiarrhythmic drugs, in Guideline IHT. http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ ucm129357.pdf
13. Health Canada (2010) Guide for the analysis and review of QT/QTc interval data. http://www.hc-sc.gc.ca/dhp-mps/alt-formats/pdf/prodpharma/applic-demande/ guide-ld/qtqtc/qt-review-examen-eng.pdf
14. Liu Q, Madabushi R, Garnett C, Booth B (2008) Experience in QT evaluation of oncology drug products since ICH E14 guidance. J Clin Oncol 26(suppl):abstr 2554
15. CAPRELSA® (vandetanib) tablets (2011) Full prescribing information. http://www1.astrazeneca-us.com/pi/caprelsa.pdf. Accessed 4 October 2012
16. Tasigna® (nilotinib) capsules (2012) Full prescribing information. http://www.pharma.us.novartis.com/product/pi/pdf/tasigna.pdf. Accessed 4 October 2012
17. VOTRIENT® (pazopanib) tablets (2012) Full prescribing information. http://us.gsk.com/products/assets/us-votrient.pdf. Accessed 4 October 2012
18. TYKERB (lapatinib) tablets (2012) Full prescribing information. http://us.gsk.com/products/assets/us-tykerb.pdf. Accessed 4 October 2012
19. Bello CL, Mulay M, Huang X, Patyna S, Dinolfo M, Levine S, Van VA, Toh M, Baum C, Rosen L (2009) Electrocardiographic characterization of the QTc interval in patients with advanced solid tumors: pharmacokinetic- pharmacodynamic evaluation of sunitinib. Clin Cancer Res 15:7045-7052
20. Tolcher AW, Appleman LJ, Shapiro GI, Mita AC, Cihon F, Mazzu A, Sundaresan PR (2011) A phase I open-label study evaluating the cardiovascular safety of sorafenib in patients with advanced cancer. Cancer Chemother Pharmacol 67:751-764
21. Sereno M, Brunello A, Chiappori A, Barriuso J, Casado E, Belda C, de Castro J, Feliu J, Gonzalez-Baron M (2008) Cardiac toxicity: old and new issues in anti-cancer drugs. Clin Transl Oncol 10:35-46
22. Brell JM (2010) Prolonged QTc interval in cancer therapeutic drug development: defining arrhythmic risk in malignancy. Prog Cardiovasc Dis 53:164-172
23. Finkle J, Bloomfield D, Uhl K, Sanhai W, Stockbridge N, Krucoff MW (2009) New precompetitive paradigms: focus on cardiac safety. Am Heart J 157:825-826
24. Morganroth J, Shah RR, Scott JW (2010) Evaluation and management of cardiac safety using the electrocardiogram in oncology clinical trials: focus on cardiac repolarization (QTc interval). Clin Pharmacol Ther 87:166-174
25. Rock EP, Finkle J, Fingert HJ, Booth BP, Garnett CE, Grant S, Justice RL, Kovacs RJ, Kowey PR, Rodriguez I, Sanhai WR, Strnadova C, Targum SL, Tsong Y, Uhl K, Stockbridge N (2009) Assessing proarrhythmic potential of drugs when optimal studies are infeasible. Am Heart J 157:827-36.e1
26. Frederica LS (1920) Dir Systolendauer in Elektrokardiogramm bei normalen Menschen und bei Herzkranken. Acta Med Scand 469-486
27. Okamoto I, Kaneda H, Satoh T, Okamoto W, Miyazaki M, Morinaga R, Ueda S, Terashima M, Tsuya A, Sarashina A, Konishi K, Arao T, Nishio K, Kaiser R, Nakagawa K (2010) Phase I safety, pharmacokinetic, and biomarker study of BIBF 1120, an oral triple tyrosine kinase inhibitor in patients with advanced solid tumors. Mol Cancer Ther 9:2825-2833
28. Bazett HC (1920) An analysis of the time-relations of electrocardiograms. Heart 353-370
29. Schmidinger M, Zielinski CC, Vogl UM, Bojic A, Bojic M, Schukro C, Ruhsam M, Hejna M, Schmidinger H (2008) Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 26:5204-5212
30. Chu TF, Rupnick MA, Kerkela R, Dallabrida SM, Zurakowski D, Nguyen L, Woulfe K, Pravda E, Cassiola F, Desai J, George S, Morgan JA, Harris DM, Ismail NS, Chen JH, Schoen FJ, Van den Abbeele AD, Demetri GD, Force T, Chen MH (2007) Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 370:2011-2019
31. Di Lorenzo G, Utorino R, Runi G, Arteni G, Icevuto E, Udini M, Icorella C, Omano C, Ieta M, Iordano A, Iuliano M, Onnella A, de Nunzio C, Izzo M, Ontesarchio V, Wer M, de Placido S (2009) Cardiovascular toxicity following sunitinib therapy in metastatic renal cell carcinoma: a multicenter analysis. Ann Oncol 20:1535-1542
32. Mego M, Reckova M, Obertova J, Sycova-Mila Z, Brozmanova K, Mardiak J (2007) Increased cardiotoxicity of sorafenib in sunitinib-pretreated patients with metastatic renal cell carcinoma. Ann Oncol 18:1906-1907
33. Telli ML, Witteles RM, Fisher GA, Srinivas S (2008) Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate. Ann Oncol 19:1613-1618
34. INLYTA® (axitinib) tablets for oral administration (2012) Full prescribing information. http://labeling.pfizer.com/ShowLabeling.aspx?id=759. Accessed 4 October 2012
35. Kropff M, Kienast J, Bisping G, Berdel WE, Gaschler-Markefski B, Stopfer P, Stefanic M, Munzert G (2009) An open-label dose-escalation study of BIBF 1120 in patients with relapsed or refractory multiple myeloma. Anticancer Res 29:4233-4238
36. Stopfer P, Rathgen K, Bischoff D, Ludtke S, Marzin K, Kaiser K, Wagner K, Ebner T (2011) Pharmacokinetics and metabolism of BIBF 1120 after oral dosing to healthy male volunteers. Xenobiotica 41:297-311
37. Ellis PM, Kaiser R, Zhao Y, Stopfer P, Gyorffy S, Hanna N (2010) Phase I open-label study of continuous treatment with BIBF 1120, a triple kinase inhibitor, and pemetrexed in pretreated non-small cell lung cancer patients. Clin Cancer Res 16:2881-2889
38. du Bois A, Huober J, Stopfer P, Pfisterer J, Wimberger P, Loibl S, Reichardt VL, Harter P (2010) 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 21:370-375
39. Sarapa N, Huang X, Varterasian M, Fingert H et al (2005) Risk management and eligibility criteria for QTc assessment in patients with advanced cancer (Abstract). J Clin Oncol 23(suppl):abstr 3047
40. Varterasian M, Meyer M, Fingert H, Radlowski D, Asbury P, Zhou X, Healey D (2003) Baseline heart rate-corrected QT and eligibility for clinical trials in oncology. J Clin Oncol 21:3378-3379