title: Pharmacokinetic drug-drug interaction study of the angiopoietin-1/angiopoietin-2-inhibiting peptibody trebananib (AMG 386) and paclitaxel in patients with advanced solid tumors.
abstract: BACKGROUND
  Trebananib is an anti-angiogenic peptibody under investigation in patients with advanced cancer. This study evaluated the pharmacokinetic (PK) drug-drug interaction of paclitaxel and trebananib.
  
  
  METHODS
  Patients with advanced solid tumors received weekly 80 mg/m(2) intravenous (IV) paclitaxel (3 weeks on/1 week off) with weekly 15 mg/kg IV trebananib starting at Week 2. Blood samples for PK analysis were collected at Week 1 (paclitaxel alone), Week 6 (paclitaxel and trebananib), and Week 8 (trebananib alone). An absence of interaction was to be concluded if the 90 % confidence intervals (CI) for the differences in paclitaxel exposure fell within the 0.80-1.25 interval.
  
  
  RESULTS
  The primary study was conducted between 7/2012 and 10/2013. Thirty-five patients were enrolled and 34 received both treatments. Most patients were white (91 %) and female (59 %); mean age was 61 years. The most common tumor types were ovarian (32 %) and bladder (27 %), 71 % of patients had stage IV disease, and all had Eastern Cooperative Oncology Group (ECOG) scores of 0 or 1. PK parameter analysis was done on patients with evaluable PK data at both assessments (with and without concomitant therapy; n = 28). The geometric least squares mean (GLSM) ratio (90 % CI) of paclitaxel AUCinf with and without trebananib was 1.17 (1.10, 1.25). The GLSM ratio (90 % CI) of trebananib AUCtau,ss with and without paclitaxel was 0.92 (0.87, 0.97). The most common adverse events were fatigue, local edema, peripheral edema, and nausea.
  
  
  CONCLUSIONS
  This study showed no evidence of clinically meaningful PK interaction between paclitaxel and trebananib.
authors.affiliation: Division of Medical Oncology, University of Colorado School of Medicine, Aurora, CO, 80045, USA, Jennifer.Diamond@ucdenver.edu.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Diamond
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wu
authors.forename: Neeraj
authors.initials: N
authors.lastname: Agarwal
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Bowles
authors.forename: Elaine T
authors.initials: ET
authors.lastname: Lam
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Werner
authors.forename: Erik
authors.initials: E
authors.lastname: Rasmussen
authors.forename: Erick
authors.initials: E
authors.lastname: Gamelin
authors.forename: Felipe
authors.initials: F
authors.lastname: Soto
authors.forename: Greg
authors.initials: G
authors.lastname: Friberg
authors.forename: Yu-Nien
authors.initials: YN
authors.lastname: Sun
authors.forename: Sunil
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042683:Angiopoietin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D042702:Angiopoietin-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000912:Antibodies, Neoplasm / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003710:Demography; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D017239:Paclitaxel / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000912:Antibodies, Neoplasm; D011993:Recombinant Fusion Proteins; D017239:Paclitaxel; C551398:trebananib