title: Phase II randomized, double-blind, placebo-controlled study of AMG 386 (trebananib) in combination with cisplatin and capecitabine in patients with metastatic gastro-oesophageal cancer.
abstract: BACKGROUND
  We evaluated AMG 386, an investigational peptibody that neutralizes the interaction between angiopoietins-1 and -2 and the Tie2 receptor, combined with cisplatin/capecitabine (CX) as first-line treatment for metastatic gastro-oesophageal cancer.
  
  
  METHODS
  Patients with metastatic gastric, gastro-oesophageal junction, or distal oesophageal adenocarcinoma were randomized 1:1:1 to CX (cisplatin 80 mg/m(2) IV Q3W; capecitabine 1000 mg/m(2) P.O. BID for 14 days Q3W) plus intravenous AMG 386 10 mg/kg QW (Arm A) or 3 mg/kg QW (Arm B), or placebo QW (Arm C). The primary end point was estimated progression-free survival (PFS).
  
  
  RESULTS
  A total of 171 patients were enrolled. Median estimated PFS in Arms A, B, and C was 4.2, 4.9, and 5.2 months, respectively (hazard ratio for Arms A+B combined versus Arm C, 0.98; 95% CI 0.67-1.43; P = 0.92). Objective response rates were 27% (Arm A), 43% (Arm B), and 35% (Arm C). Incidence of grade ≥3 adverse events was 80% in Arm A, 84% in Arm B, and 75% in Arm C. There was no evidence of pharmacokinetic interactions.
  
  
  CONCLUSIONS
  In this study, PFS and ORR were estimated to be similar with AMG 386 plus CX and placebo plus CX treatment. Compared with placebo, toxicity of AMG 386 plus CX was greater but manageable.
  The results of this study have not been previously published or submitted for publication elsewhere. The results were presented in part at the Gastrointestinal Cancers Symposium, San Francisco, CA, January 20-22, 2011.
  
  
  BACKGROUND
  ClinicalTrials.gov registration number: NCT00583674.
authors.affiliation: Department of Oncology, Belfast City Hospital, Belfast BT9 7AB, Northern Ireland. martin.eatock@belfasttrust.hscni.net
authors.forename: M M
authors.initials: MM
authors.lastname: Eatock
authors.forename: N C
authors.initials: NC
authors.lastname: Tebbutt
authors.forename: C L
authors.initials: CL
authors.lastname: Bampton
authors.forename: A H
authors.initials: AH
authors.lastname: Strickland
authors.forename: M
authors.initials: M
authors.lastname: Valladares-Ayerbes
authors.forename: A
authors.initials: A
authors.lastname: Swieboda-Sadlej
authors.forename: E
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: N
authors.initials: N
authors.lastname: Nanayakkara
authors.forename: Y-N
authors.initials: YN
authors.lastname: Sun
authors.forename: Z D
authors.initials: ZD
authors.lastname: Zhong
authors.forename: M B
authors.initials: MB
authors.lastname: Bass
authors.forename: A H
authors.initials: AH
authors.lastname: Adewoye
authors.forename: G
authors.initials: G
authors.lastname: Bodoky
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000069287:Capecitabine; D002318:Cardiovascular Diseases / Q000139:chemically induced; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D011993:Recombinant Fusion Proteins; D003841:Deoxycytidine; D000069287:Capecitabine; D002945:Cisplatin; D005472:Fluorouracil; C551398:trebananib