PMID- 25019569
OWN - NLM
STAT- MEDLINE
DCOM- 20141222
LR  - 20181202
IS  - 1095-6859 (Electronic)
IS  - 0090-8258 (Linking)
VI  - 135
IP  - 1
DP  - 2014 Oct
TI  - A phase 1b study of trebananib in combination with pegylated liposomal 
      doxorubicin or topotecan in women with recurrent platinum-resistant or partially 
      platinum-sensitive ovarian cancer.
PG  - 25-33
LID - S0090-8258(14)01078-6 [pii]
LID - 10.1016/j.ygyno.2014.07.003 [doi]
AB  - OBJECTIVE: To examine the tolerability and antitumor activity of trebananib plus 
      pegylated liposomal doxorubicin (PLD) or topotecan in recurrent 
      platinum-resistant or partially platinum-sensitive ovarian cancer. METHODS: In 
      this open-label phase 1b study, patients received trebananib 10 mg/kg or 15 mg/kg 
      IV QW plus PLD 50 mg/m(2) (cohorts A1 and A3, respectively) or topotecan 4 
      mg/m(2) (cohorts B1 and B3, respectively). Endpoints were dose-limiting toxicity 
      (DLT; primary); treatment-emergent adverse events (AEs), overall response rate, 
      anti-trebananib antibodies, and pharmacokinetics (secondary). RESULTS: 103 
      patients were enrolled. One patient in A1 and B1 had DLTs. Across all cohorts, 
      the most common AEs were nausea, fatigue, and peripheral edema. Across both 
      trebananib plus PLD cohorts (A1/A3), grade 4 AEs were pulmonary embolism, disease 
      progression, and anemia. Two patients had grade 5 intestinal perforation (n=1) 
      and sudden death (n=1). Across both trebananib plus topotecan cohorts (B1/B3), 
      grade 4 AEs were neutropenia, hypokalemia, decreased granulocyte count, chest 
      pain, dyspnea, decreased neutrophil count, and pulmonary embolism. Two patients 
      had grade 5 disease progression. One patient had grade 5 pleural effusion 
      associated with progressive disease. Confirmed objective response rates were 
      36.0% (A1), 34.8% (A3), 16.7% (B1), and 0.0% (B3). Median progression-free 
      survival duration (months) was 7.4 (A1), 7.1 (A3), 3.5 (B1), and 3.1 (B3), 
      respectively. No drug-drug interactions were apparent. CONCLUSIONS: Trebananib 
      10mg/kg and 15 mg/kg IV QW plus PLD or topotecan appear to have acceptable 
      toxicity profiles in recurrent platinum-resistant or partially platinum-sensitive 
      ovarian cancer. Antitumor activity was evident across all cohorts.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Vergote, Ignace
AU  - Vergote I
AD  - University Hospitals Leuven and KU Leuven, Leuven, Belgium.
FAU - Schilder, Russell J
AU  - Schilder RJ
AD  - Thomas Jefferson University, Philadelphia, PA, USA.
FAU - Pippitt, Charles H Jr
AU  - Pippitt CH Jr
AD  - Novant Health Oncology Specialists, Winston-Salem, NC, USA.
FAU - Wong, Shirley
AU  - Wong S
AD  - Western Hospital, Footscray, VIC, Australia.
FAU - Gordon, Alan N
AU  - Gordon AN
AD  - Emory University, Atlanta, GA, USA.
FAU - Scudder, Sidney
AU  - Scudder S
AD  - UC Davis Comprehensive Cancer Center, Sacramento, CA, USA.
FAU - Kridelka, Frederic
AU  - Kridelka F
AD  - Centre Hospitalier Universitaire de Liege Sart Tilman, Liege, Belgium.
FAU - Dirix, Luc
AU  - Dirix L
AD  - Sint Augustinus, Antwerpen, Belgium.
FAU - Leach, Joseph W
AU  - Leach JW
AD  - Virginia Piper Cancer Institute, Minneapolis, MN, USA.
FAU - Ananda, Sumitra
AU  - Ananda S
AD  - Royal Women's Hospital, Melbourne, VIC, Australia.
FAU - Nanayakkara, Nuwan
AU  - Nanayakkara N
AD  - Quintiles, San Diego, CA, USA.
FAU - Melara, Rebeca
AU  - Melara R
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Bass, Michael B
AU  - Bass MB
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Litten, Jason
AU  - Litten J
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Adewoye, Henry
AU  - Adewoye H
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Wenham, Robert M
AU  - Wenham RM
AD  - H. Lee Moffitt Cancer Center, Tampa, FL, USA. Electronic address: 
      Robert.Wenham@moffitt.org.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140711
PL  - United States
TA  - Gynecol Oncol
JT  - Gynecologic oncology
JID - 0365304
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Platinum Compounds)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Topoisomerase I Inhibitors)
RN  - 0 (liposomal doxorubicin)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 7M7YKX2N15 (Topotecan)
RN  - 80168379AG (Doxorubicin)
RN  - X8Y5U6NC7E (trebananib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Angiogenesis Inhibitors/*administration & dosage/adverse effects
MH  - Antibiotics, Antineoplastic/*administration & dosage/adverse effects
MH  - Doxorubicin/administration & dosage/adverse effects/*analogs & derivatives
MH  - Drug Resistance, Neoplasm
MH  - Drug Therapy, Combination
MH  - Female
MH  - Humans
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*drug therapy
MH  - Ovarian Neoplasms/*drug therapy
MH  - Platinum Compounds/adverse effects/*therapeutic use
MH  - Polyethylene Glycols/administration & dosage/adverse effects
MH  - Recombinant Fusion Proteins/*administration & dosage/adverse effects
MH  - Topoisomerase I Inhibitors/*administration & dosage/adverse effects
MH  - Topotecan/*administration & dosage/adverse effects
OTO - NOTNLM
OT  - Angiogenesis
OT  - Angiopoietins
OT  - Combination treatments
OT  - Dose-limiting toxicities
OT  - Targeted therapy
OT  - Tie2 receptor
EDAT- 2014/07/16 06:00
MHDA- 2014/12/23 06:00
CRDT- 2014/07/15 06:00
PHST- 2014/04/23 00:00 [received]
PHST- 2014/07/03 00:00 [revised]
PHST- 2014/07/06 00:00 [accepted]
PHST- 2014/07/15 06:00 [entrez]
PHST- 2014/07/16 06:00 [pubmed]
PHST- 2014/12/23 06:00 [medline]
AID - S0090-8258(14)01078-6 [pii]
AID - 10.1016/j.ygyno.2014.07.003 [doi]
PST - ppublish
SO  - Gynecol Oncol. 2014 Oct;135(1):25-33. doi: 10.1016/j.ygyno.2014.07.003. Epub 2014 
      Jul 11.