PMID- 22692704
OWN - NLM
STAT- MEDLINE
DCOM- 20130205
LR  - 20220408
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 118
IP  - 24
DP  - 2012 Dec 15
TI  - AMG 386 in combination with sorafenib in patients with metastatic clear cell 
      carcinoma of the kidney: a randomized, double-blind, placebo-controlled, phase 2 
      study.
PG  - 6152-61
LID - 10.1002/cncr.27632 [doi]
AB  - BACKGROUND: This study evaluated the tolerability and antitumor activity of AMG 
      386, a peptibody (a peptide Fc fusion) that neutralizes the interaction of 
      angiopoietin-1 and angiopoietin-2 with Tie2 (tyrosine kinase with 
      immunoglobulin-like and EGF-like domains 2), plus sorafenib in patients with 
      clear cell metastatic renal cell carcinoma (mRCC) in a randomized controlled 
      study. METHODS: Previously untreated patients with mRCC were randomized 1:1:1 to 
      receive sorafenib 400 mg orally twice daily plus intravenous AMG 386 at 10 mg/kg 
      (arm A) or 3 mg/kg (arm B) or placebo (arm C) once weekly (qw). Patients in arm C 
      could receive open-label AMG 386 at 10 mg/kg qw plus sorafenib following disease 
      progression. The primary endpoint was progression-free survival (PFS). RESULTS: A 
      total of 152 patients were randomized. Median PFS was 9.0, 8.5, and 9.0 months in 
      arms A, B, and C, respectively (hazard ratio for arms A and B vs arm C, 0.88; 95% 
      confidence interval [CI], 0.60-1.30; P = .523). The objective response rate (95% 
      CI) for arms A, B, and C, respectively, was 38% (25%-53%), 37% (24%-52%), and 25% 
      (14%-40%). Among 30 patients in arm C who had disease progression and 
      subsequently received open-label AMG 386 at 10 mg/kg qw, the objective response 
      rate was 3% (95% CI, 0%-17%). Frequently occurring adverse events (AEs) included 
      diarrhea (arms A/B/C, 70%/67%/56%), palmar-plantar erythrodysesthesia syndrome 
      (52%/47%/54%), alopecia (50%/45%/50%), and hypertension (42%/49%/46%). Fifteen 
      patients had grade 4 AEs (arms A/B/C, n = 3/7/5); 4 had fatal AEs (n = 2/1/1), 
      with 1 (abdominal pain, arm B) considered possibly related to AMG 386. 
      CONCLUSIONS: In patients with mRCC, AMG 386 plus sorafenib was tolerable but did 
      not significantly improve PFS compared with placebo plus sorafenib.
CI  - Copyright (c) 2012 American Cancer Society.
FAU - Rini, Brian
AU  - Rini B
AD  - The Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195, USA. 
      rinib2@ccf.org
FAU - Szczylik, Cezary
AU  - Szczylik C
FAU - Tannir, Nizar M
AU  - Tannir NM
FAU - Koralewski, Piotr
AU  - Koralewski P
FAU - Tomczak, Piotr
AU  - Tomczak P
FAU - Deptala, Andrzej
AU  - Deptala A
FAU - Dirix, Luc Y
AU  - Dirix LY
FAU - Fishman, Mayer
AU  - Fishman M
FAU - Ramlau, Rodryg
AU  - Ramlau R
FAU - Ravaud, Alain
AU  - Ravaud A
FAU - Rogowski, Wojciech
AU  - Rogowski W
FAU - Kracht, Karolyn
AU  - Kracht K
FAU - Sun, Yu-Nien
AU  - Sun YN
FAU - Bass, Michael B
AU  - Bass MB
FAU - Puhlmann, Markus
AU  - Puhlmann M
FAU - Escudier, Bernard
AU  - Escudier B
LA  - eng
SI  - ClinicalTrials.gov/NCT00467025
GR  - P30 CA076292/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120612
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzenesulfonates)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Pyridines)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 9ZOQ3TZI87 (Sorafenib)
RN  - X8Y5U6NC7E (trebananib)
RN  - Clear-cell metastatic renal cell carcinoma
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols
MH  - Benzenesulfonates/*therapeutic use
MH  - Biomarkers, Tumor/metabolism
MH  - Carcinoma, Renal Cell/*drug therapy/mortality/secondary
MH  - Double-Blind Method
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Kidney Neoplasms/*drug therapy/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Niacinamide/analogs & derivatives
MH  - Phenylurea Compounds
MH  - Prognosis
MH  - Pyridines/*therapeutic use
MH  - Recombinant Fusion Proteins/*therapeutic use
MH  - Sorafenib
MH  - Survival Rate
PMC - PMC4666535
MID - NIHMS737796
COIS- CONFLICT OF INTEREST DISCLOSURE Dr. Rini has been a consultant for and has 
      received research funding from Amgen. Dr. Tannir has been a consultant and has 
      received honoraria from Pfizer, Abbott, and Novartis, and has received research 
      funding from Abbott, Amgen, and Pfizer. Dr. Fishman has been a consultant for 
      Aveo, Eisai, GlaxoSmithKline, Genentech, Seattle Genetics, Pfizer, Novartis, 
      Prometheus, and Altor, has received honoraria from Aveo, Bayer, Pfizer, Novartis, 
      Genentech, Eisai, and GlaxoSmithKline, and research funding from Amgen, Altor, 
      Aveo, FDA, NCI, Southwest Oncology Group, Bayer, Pfizer, Genentech, and Eli 
      Lilly. Dr. Escudier has been a consultant for Bayer, Pfizer, and Roche, and has 
      received honoraria from Bayer, Roche, Pfizer, Genentech, Novartis, and Aveo. Ms. 
      Kracht and Drs. Sun, Bass, and Puhlmann are Amgen employees/shareholders. Dr. 
      Ravaud has been a consultant for Pfizer, Novartis, Bayer, GlaxoSmithKline, 
      Dendreon, and Aveo, has received travel expenses from Novartis and Pfizer, and 
      research funding from Pfizer and Roche. All other authors made no disclosures.
EDAT- 2012/06/14 06:00
MHDA- 2013/02/06 06:00
PMCR- 2015/12/01
CRDT- 2012/06/14 06:00
PHST- 2012/02/15 00:00 [received]
PHST- 2012/04/12 00:00 [accepted]
PHST- 2012/06/14 06:00 [entrez]
PHST- 2012/06/14 06:00 [pubmed]
PHST- 2013/02/06 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - 10.1002/cncr.27632 [doi]
PST - ppublish
SO  - Cancer. 2012 Dec 15;118(24):6152-61. doi: 10.1002/cncr.27632. Epub 2012 Jun 12.