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 |
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| Institution: | 1. University Hospitals-KU Leuven, Leuven Cancer Institute, Department of Obstetrics and Gynecology, Herestraat 49, B-3000 Leuven, Belgium;2. 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;3. Université Catholique de Louvain, Centre du Cancer, Service d’Oncologie Médicale des Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, Bruxelles 1200, Belgium;4. Royal Women’s Hospital, Oncology Unit, 20 Flemington Road, Parkville 3052, VIC, Australia;5. Western Hospital, Department of Medical Oncology, Oncology Research Level 2 South, Gordon Street, Footscray 3011, VIC, Australia;6. Amgen Inc., Department of Biostatistics, One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA;7. Amgen Inc., Department of Pharmacokinetics and Drug Metabolism, One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA;8. Amgen Inc., Department of Clinical Immunology and Biological Sample Management, One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA;9. Amgen Inc., Department of Clinical Development, One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA;10. Hospital Universitario Clínico San Carlos, Servicio de Oncologia Medica, Calle del Professor Martín Lagos s/n, Madrid 28040, Spain;1. Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, United Kingdom;2. William Harvey Hospital, Ashford, Kent TN24 0LZ, United Kingdom;3. Woolfson Institute of Preventative Medicine, Charterhouse Sq., London EC1M 6BQ, United Kingdom;4. Division of Cancer Studies, King’s College London, 3rd Floor Bermondsey Wing, Guy’s Hospital, London SE1 9RT, United Kingdom;1. Orthopaedics and Traumatology Department, University Hospital of Nantes CHU, Hôtel-Dieu, 44 093 Nantes Cedex, France;2. LPRO, Inserm U957, UFR Médecine, Université de Nantes, 1 Rue Gaston Veil, 44000 Nantes, France;3. Univeristy Hospital de la Conception, 147 Bd Baille, 13005 Marseille, France;4. University Hospital de Hautepierre, Av. Molière, 67 000 Strasbourg, France;5. University Hospital Trousseau, Rue des Loches, 37 004 Tours, France;6. University Hospital of Purpan, Place du Dr. Baylac, 31 059 Toulouse, France;7. University Hospital Dupuytren, Av. Martin Luther King, 87 042 Limoges, France;8. University Hospital of Cochin-Port Royal, Av. Du Fb Saint Jacques, 75 014 Paris, France;1. MRC Centre for Reproductive Health, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK;2. Edinburgh Breast Unit and Edinburgh University Cancer Research Centre, Western General Hospital, Edinburgh, UK;1. Department of Surgery, Erasmus Medical Center, Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands;2. Department of Epidemiology, Erasmus Medical Center, Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands;3. The Health Care Inspectorate, The Hague, The Netherlands;1. Center for Applied Medical Research, University of Navarra, 331008 Pamplona, Spain |
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| Abstract: | AimTo 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.MethodsIn this open-label phase 1b study, patients received intravenous (IV) trebananib 15 mg/kg administered weekly (QW) plus paclitaxel 175 mg/m2 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).ResultsTwenty 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.ConclusionsIn 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. |
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| Keywords: | Angiogenesis inhibitors Angiopoietin-1 Angiopoietin-2 Tie2 receptor Combination drug therapy |
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