PMID- 22184370
OWN - NLM
STAT- MEDLINE
DCOM- 20120508
LR  - 20220311
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 30
IP  - 4
DP  - 2012 Feb 1
TI  - Randomized, double-blind, placebo-controlled phase II study of AMG 386 combined 
      with weekly paclitaxel in patients with recurrent ovarian cancer.
PG  - 362-71
LID - 10.1200/JCO.2010.34.3178 [doi]
AB  - PURPOSE: To estimate the efficacy and toxicity of AMG 386, an investigational 
      peptide-Fc fusion protein that neutralizes the interaction between the Tie2 
      receptor and angiopoietin-1/2, plus weekly paclitaxel in patients with recurrent 
      ovarian cancer. PATIENTS AND METHODS: Patients with recurrent epithelial ovarian, 
      fallopian tube, or primary peritoneal cancer were randomly assigned 1:1:1 to 
      receive paclitaxel (80 mg/m(2) once weekly [QW], 3 weeks on/1 week off) plus 
      intravenous AMG 386 10 mg/kg QW (arm A), AMG 386 3 mg/kg QW (arm B), or placebo 
      QW (arm C). The primary end point was progression-free survival (PFS). Secondary 
      end points included overall survival, objective response, CA-125 response, 
      safety, and pharmacokinetics. RESULTS: One hundred sixty-one patients were 
      randomly assigned. Median PFS was 7.2 months (95% CI, 5.3 to 8.1 months) in arm 
      A, 5.7 months (95% CI, 4.6 to 8.0 months) in arm B, and 4.6 months (95% CI, 1.9 
      to 6.7 months) in arm C. The hazard ratio for arms A and B combined versus arm C 
      was 0.76 (95% CI, 0.52 to 1.12; P = .165). Further analyses suggested an 
      exploratory dose-response effect for PFS across arms (Tarone's test, P = .037). 
      Objective response rates for arms A, B, and C were 37%, 19%, and 27%, 
      respectively. The incidence of grade >/= 3 adverse events (AEs) in arms A, B, and C 
      was 65%, 55%, and 64%, respectively. Frequent AEs included hypertension (8%, 6%, 
      and 5% in arms A, B, and C, respectively), peripheral edema (71%, 51%, and 22% in 
      arms A, B, and C, respectively), and hypokalemia (21%, 15%, and 5% in arms A, B, 
      and C, respectively). AMG 386 exhibited linear pharmacokinetic properties at the 
      tested doses. CONCLUSION: AMG 386 combined with weekly paclitaxel was tolerable, 
      with a manageable and distinct toxicity profile. The data suggest evidence of 
      antitumor activity and a dose-response effect, warranting further studies in 
      ovarian cancer.
FAU - Karlan, Beth Y
AU  - Karlan BY
AD  - Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Beth.Karlan@cshs.org
FAU - Oza, Amit M
AU  - Oza AM
FAU - Richardson, Gary E
AU  - Richardson GE
FAU - Provencher, Diane M
AU  - Provencher DM
FAU - Hansen, Vincent L
AU  - Hansen VL
FAU - Buck, Martin
AU  - Buck M
FAU - Chambers, Setsuko K
AU  - Chambers SK
FAU - Ghatage, Prafull
AU  - Ghatage P
FAU - Pippitt, Charles H Jr
AU  - Pippitt CH Jr
FAU - Brown, John V 3rd
AU  - Brown JV 3rd
FAU - Covens, Allan
AU  - Covens A
FAU - Nagarkar, Raj V
AU  - Nagarkar RV
FAU - Davy, Margaret
AU  - Davy M
FAU - Leath, Charles A 3rd
AU  - Leath CA 3rd
FAU - Nguyen, Hoa
AU  - Nguyen H
FAU - Stepan, Daniel E
AU  - Stepan DE
FAU - Weinreich, David M
AU  - Weinreich DM
FAU - Tassoudji, Marjan
AU  - Tassoudji M
FAU - Sun, Yu-Nien
AU  - Sun YN
FAU - Vergote, Ignace B
AU  - Vergote IB
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20111219
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Recombinant Fusion Proteins)
RN  - P88XT4IS4D (Paclitaxel)
RN  - X8Y5U6NC7E (trebananib)
SB  - IM
CIN - J Clin Oncol. 2012 Feb 1;30(4):345-7. PMID: 22184398
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Disease-Free Survival
MH  - Double-Blind Method
MH  - Fallopian Tube Neoplasms/drug therapy
MH  - Female
MH  - Humans
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*drug therapy/pathology
MH  - Ovarian Neoplasms/*drug therapy/pathology
MH  - Paclitaxel/administration & dosage/adverse effects
MH  - Peritoneal Neoplasms/drug therapy
MH  - Recombinant Fusion Proteins/administration & dosage/adverse effects
MH  - Survival Analysis
EDAT- 2011/12/21 06:00
MHDA- 2012/05/09 06:00
CRDT- 2011/12/21 06:00
PHST- 2011/12/21 06:00 [entrez]
PHST- 2011/12/21 06:00 [pubmed]
PHST- 2012/05/09 06:00 [medline]
AID - JCO.2010.34.3178 [pii]
AID - 10.1200/JCO.2010.34.3178 [doi]
PST - ppublish
SO  - J Clin Oncol. 2012 Feb 1;30(4):362-71. doi: 10.1200/JCO.2010.34.3178. Epub 2011 
      Dec 19.