PMID- 25037684 OWN - NLM STAT- MEDLINE DCOM- 20150102 LR - 20151119 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 50 IP - 14 DP - 2014 Sep TI - A phase 1b, open-label study of trebananib in combination with paclitaxel and carboplatin in patients with ovarian cancer receiving interval or primary debulking surgery. PG - 2408-16 LID - S0959-8049(14)00754-0 [pii] LID - 10.1016/j.ejca.2014.06.010 [doi] AB - AIM: To evaluate the tolerability, pharmacokinetics and tumour response of first-line trebananib plus paclitaxel and carboplatin followed by trebananib maintenance in high-risk or advanced ovarian cancer. METHODS: In this open-label phase 1b study, patients received intravenous (IV) trebananib 15 mg/kg administered weekly (QW) plus paclitaxel 175 mg/m(2) once every 3 weeks (Q3W) and carboplatin 6 mg/mL . min Q3W followed by trebananib 15 mg/kg QW monotherapy for 18 months. End-points were dose-limiting toxicities (DLTs; primary); treatment-emergent adverse events (AEs), anti-trebananib antibodies, pharmacokinetics and tumour response (secondary). RESULTS: Twenty seven patients (interval debulking surgery [IDS], n=13) were enrolled. No DLTs occurred. During the combination therapy phase, AEs (>50%) in patients with IDS were nausea, diarrhoea, fatigue, decreased appetite and thrombocytopenia. In patients with primary debulking surgery (PDS), they were nausea, diarrhoea, fatigue and localised oedema. Grade 4 AEs were neutropenia (IDS, PDS; all n=3) and thrombocytopenia (IDS, PDS; all n=1). No deaths occurred. Toxicity results pertaining to trebananib maintenance were immature. The treatment combination did not markedly affect the pharmacokinetics across agents. In patients with IDS (n=14 after one patient was reassigned from PDS to IDS), 12 patients had a partial response (PR), two patients had stable disease. In patients with PDS (n=4), three patients had a complete response, one patient had a PR. CONCLUSIONS: In women with ovarian cancer receiving IDS or PDS, IV trebananib 15 mg/kg QW plus paclitaxel and carboplatin appears tolerable. Results suggest that the treatment combination followed by trebananib 15 mg/kg monotherapy is associated with antitumour activity. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Vergote, I AU - Vergote I AD - University Hospitals-KU Leuven, Leuven Cancer Institute, Department of Obstetrics and Gynecology, Herestraat 49, B-3000 Leuven, Belgium. Electronic address: Ignace.Vergote@uz.kuleuven.ac.be. FAU - Oaknin, A AU - Oaknin A AD - Vall d'Hebron University Hospital, Medical Oncology Department, and Vall d'Hebron Institute of Oncology (VHIO), Head, Neck, and Gynecological Tumors Group, P. Vall d'Hebron 119-129, Barcelona 08035, Spain. Electronic address: aoaknin@gmail.com. FAU - Baurain, J-F AU - Baurain JF AD - Universite Catholique de Louvain, Centre du Cancer, Service d'Oncologie Medicale des Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, Bruxelles 1200, Belgium. Electronic address: jean-francois.baurain@uclouvain.be. FAU - Ananda, S AU - Ananda S AD - Royal Women's Hospital, Oncology Unit, 20 Flemington Road, Parkville 3052, VIC, Australia. Electronic address: Sumitra.Ananda@mh.org.au. FAU - Wong, S AU - Wong S AD - Western Hospital, Department of Medical Oncology, Oncology Research Level 2 South, Gordon Street, Footscray 3011, VIC, Australia. Electronic address: shirleyS.wong@mh.org.au. FAU - Su, X AU - Su X AD - Amgen Inc., Department of Biostatistics, One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. Electronic address: xsu@amgen.com. FAU - Wu, B AU - Wu B AD - Amgen Inc., Department of Pharmacokinetics and Drug Metabolism, One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. Electronic address: wub@amgen.com. FAU - Zhong, Z AU - Zhong Z AD - Amgen Inc., Department of Clinical Immunology and Biological Sample Management, One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. Electronic address: zhongz@amgen.com. FAU - Warner, D AU - Warner D AD - Amgen Inc., Department of Clinical Development, One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. Electronic address: djwarner@amgen.com. FAU - Casado, A AU - Casado A AD - Hospital Universitario Clinico San Carlos, Servicio de Oncologia Medica, Calle del Professor Martin Lagos s/n, Madrid 28040, Spain. Electronic address: Acasado.hcsc@salud.madrid.org. LA - eng SI - ClinicalTrials.gov/NCT01253681 PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20140715 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Recombinant Fusion Proteins) RN - BG3F62OND5 (Carboplatin) RN - P88XT4IS4D (Paclitaxel) RN - X8Y5U6NC7E (trebananib) SB - IM MH - Adult MH - Aged MH - Angiogenesis Inhibitors/administration & dosage/pharmacokinetics MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects/pharmacokinetics MH - Carboplatin/administration & dosage/pharmacokinetics MH - Cohort Studies MH - Combined Modality Therapy MH - Female MH - Humans MH - Middle Aged MH - Ovarian Neoplasms/*drug therapy/metabolism/*surgery MH - Paclitaxel/administration & dosage/pharmacokinetics MH - Recombinant Fusion Proteins/administration & dosage/pharmacokinetics MH - Treatment Outcome OTO - NOTNLM OT - Angiogenesis inhibitors OT - Angiopoietin-1 OT - Angiopoietin-2 OT - Combination drug therapy OT - Tie2 receptor EDAT- 2014/07/20 06:00 MHDA- 2015/01/03 06:00 CRDT- 2014/07/20 06:00 PHST- 2014/04/16 00:00 [received] PHST- 2014/06/10 00:00 [revised] PHST- 2014/06/13 00:00 [accepted] PHST- 2014/07/20 06:00 [entrez] PHST- 2014/07/20 06:00 [pubmed] PHST- 2015/01/03 06:00 [medline] AID - S0959-8049(14)00754-0 [pii] AID - 10.1016/j.ejca.2014.06.010 [doi] PST - ppublish SO - Eur J Cancer. 2014 Sep;50(14):2408-16. doi: 10.1016/j.ejca.2014.06.010. Epub 2014 Jul 15.