PMID- 26171911
OWN - NLM
STAT- MEDLINE
DCOM- 20151229
LR  - 20240324
IS  - 1095-6859 (Electronic)
IS  - 0090-8258 (Print)
IS  - 0090-8258 (Linking)
VI  - 138
IP  - 3
DP  - 2015 Sep
TI  - A phase II trial of trebananib (AMG 386; IND#111071), a selective angiopoietin 
      1/2 neutralizing peptibody, in patients with persistent/recurrent carcinoma of 
      the endometrium: An NRG/Gynecologic Oncology Group trial.
PG  - 513-8
LID - S0090-8258(15)30069-X [pii]
LID - 10.1016/j.ygyno.2015.07.006 [doi]
AB  - OBJECTIVES: Ang1 & 2 (angiopoietin-1; -2) interact with Tie2 receptors on 
      endothelial cells to mediate vascular remodeling in an angiogenesis signaling 
      pathway distinct from the VEGF axis. Trebananib is a peptide Fc fusion protein 
      that binds Ang1 and 2 and prevents interaction with Tie2. The efficacy of 
      trebananib in recurrent/persistent endometrial cancer (EC) was studied. METHODS: 
      The primary objective was to determine the frequency of patients with objective 
      tumor responses (ORR) and event-free survival for >/=6months (6-month EFS) and 
      determine toxicity of trebananib at a dose and schedule of 15mg/kg, IV QW. 
      Recurrent/persistent EC, measurable disease, and </=2 prior chemotherapy lines were 
      required. RESULTS: Thirty-two patients were eligible and treated. The most common 
      histologies were G1/2 endometrioid (31%), G3 endometrioid (28%) and serous 
      (31.3%). 78% of patients had 1 prior regimen. Patients received 1-9+ cycles of 
      trebananib; 24 patients (75%) received </=2cycles. One patient had a partial 
      response (3.1%); 8 patients had stable disease (25%) and 5 patients (15.6%) had 6 
      month EFS. Median progression-free survival and overall-survival were 1.97 months 
      (90% CI 1.77-2.1) and 6.6 months (90% CI 4.01-14.75), respectively. Most common 
      adverse events (AEs) were fatigue, anemia, and GI issues. Grade 3 and 4 AEs were: 
      GI 31 and 0%; vascular 22 and 0%; metabolism/nutrition 19 and 3%; and general 
      (including edema) 16 and 0%. CONCLUSIONS: Trebananib has insufficient single 
      agent activity in recurrent EC to warrant further investigation at this 
      dose/schedule.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Moore, Kathleen N
AU  - Moore KN
AD  - Stephenson Oklahoma Cancer Center, 800 NE 10th Street, Oklahoma City, OK 73104, 
      United States. Electronic address: Kathleen-Moore@ouhsc.edu.
FAU - Sill, Michael W
AU  - Sill MW
AD  - NRG Oncology Statistics & Data Management Center, Roswell Park Cancer Institute, 
      Elm and Carlton Streets, Buffalo, NY 14263, United States. Electronic address: 
      msill@gogstats.org.
FAU - Tenney, Meaghan E
AU  - Tenney ME
AD  - University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, United States. 
      Electronic address: mtenney@babies.bsd.uchicago.edu.
FAU - Darus, Christopher J
AU  - Darus CJ
AD  - Maine Medical Center, 102 Campus Drive Unit 116, Scarborough, ME 04074, United 
      States. Electronic address: darusc@mmc.org.
FAU - Griffin, David
AU  - Griffin D
AD  - Upstate Carolina CCOP Oncology Research, 101 East Wood Street, Spartanburg, SC 
      29303, United States. Electronic address: david_griffin@bshsi.org.
FAU - Werner, Theresa L
AU  - Werner TL
AD  - Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake 
      City, UT 84112, United States. Electronic address: theresa.werner@hci.utah.edu.
FAU - Rose, Peter G
AU  - Rose PG
AD  - Cleveland Clinic Foundation, 9500 Euclid Avenue, A81, Cleveland, OH 44106, United 
      States. Electronic address: rosep@ccf.org.
FAU - Behrens, Robert
AU  - Behrens R
AD  - Cancer Center of Iowa, Iowa Wide Oncology Research Coalition, 1221 Pleasant 
      Street, Suite 450, Des Moines IA 50309, United States. Electronic address: 
      rbehrens@cancercenterofiowa.com.
LA  - eng
GR  - U10 CA180868/CA/NCI NIH HHS/United States
GR  - 1 U10 CA180822/CA/NCI NIH HHS/United States
GR  - CA 27469/CA/NCI NIH HHS/United States
GR  - U10 CA027469/CA/NCI NIH HHS/United States
GR  - U10 CA037517/CA/NCI NIH HHS/United States
GR  - CA 37517/CA/NCI NIH HHS/United States
GR  - U10 CA180822/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150711
PL  - United States
TA  - Gynecol Oncol
JT  - Gynecologic oncology
JID - 0365304
RN  - 0 (ANGPT1 protein, human)
RN  - 0 (ANGPT2 protein, human)
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Angiopoietin-1)
RN  - 0 (Angiopoietin-2)
RN  - 0 (Recombinant Fusion Proteins)
RN  - X8Y5U6NC7E (trebananib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Angiogenesis Inhibitors/adverse effects/*therapeutic use
MH  - Angiopoietin-1/antagonists & inhibitors/metabolism
MH  - Angiopoietin-2/antagonists & inhibitors/metabolism
MH  - Endometrial Neoplasms/blood supply/*drug therapy/metabolism
MH  - Female
MH  - Humans
MH  - Middle Aged
MH  - Recombinant Fusion Proteins/adverse effects/*therapeutic use
PMC - PMC4692151
MID - NIHMS710760
OTO - NOTNLM
OT  - Angiogenesis
OT  - Endometrial cancer
OT  - NCT01210222
OT  - Trebananib
EDAT- 2015/07/15 06:00
MHDA- 2015/12/30 06:00
PMCR- 2016/09/01
CRDT- 2015/07/15 06:00
PHST- 2015/05/27 00:00 [received]
PHST- 2015/07/06 00:00 [accepted]
PHST- 2015/07/15 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2015/12/30 06:00 [medline]
PHST- 2016/09/01 00:00 [pmc-release]
AID - S0090-8258(15)30069-X [pii]
AID - 10.1016/j.ygyno.2015.07.006 [doi]
PST - ppublish
SO  - Gynecol Oncol. 2015 Sep;138(3):513-8. doi: 10.1016/j.ygyno.2015.07.006. Epub 2015 
      Jul 11.