title: Randomized phase II placebo-controlled trial of maintenance therapy using the oral triple angiokinase inhibitor BIBF 1120 after chemotherapy for relapsed ovarian cancer.
abstract: OBJECTIVE
  Inhibiting angiogenesis is one of the most promising avenues for new therapies for ovarian cancer. We investigated the efficacy and safety of a novel agent, BIBF 1120, a triple angiokinase inhibitor, after chemotherapy for relapsed disease.
  
  
  METHODS
  We conducted a randomized, double-blind, controlled phase II trial in 83 patients who had just completed chemotherapy for relapsed ovarian cancer, with evidence of response, but at high risk of further early recurrence. The patients were randomly assigned to receive maintenance therapy using BIBF 1120 250 mg or placebo, twice per day, continuously for 36 weeks. End points were progression-free survival (PFS), toxicity, and overall survival.
  
  
  RESULTS
  Thirty-six-week PFS rates were 16.3% and 5.0% in the BIBF 1120 and placebo groups, respectively (hazard ratio, 0.65; 95% CI, 0.42 to 1.02; P = .06). Four patients continued on BIBF 1120, including two patients for another year or more. The proportion of patients with any grade 3 or 4 adverse events was similar between the groups (34.9% for BIBF 1120 v 27.5% for placebo; P = .49; mostly grade 3). However, more patients on BIBF 1120 experienced diarrhea, nausea, or vomiting (mainly grade 1 or 2 and no grade 4). There was a higher rate of grade 3 or 4 hepatotoxicity in patients on BIBF 1120 (51.2%) compared with patients on placebo (7.5%; P < .001), but this was rarely of clinical significance, and patients continued with the trial treatment. A single-level dose reduction to 150 mg was made in 15 patients, all on active drug.
  
  
  CONCLUSIONS
  BIBF 1120 is well tolerated and associated with a potential improvement in PFS. The observed treatment effect is sufficient to justify further study within a large phase III trial.
authors.affiliation: Cancer Research UK and University College London Cancer Trials Centre, UCL Cancer Institute, University College London, 90 Tottenham Court Rd, London W1T 4TJ. j.ledermann@ctc.ucl.ac.uk
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Ledermann
authors.forename: Allan
authors.initials: A
authors.lastname: Hackshaw
authors.forename: Stan
authors.initials: S
authors.lastname: Kaye
authors.forename: Gordon
authors.initials: G
authors.lastname: Jayson
authors.forename: Hani
authors.initials: H
authors.lastname: Gabra
authors.forename: Iain
authors.initials: I
authors.lastname: McNeish
authors.forename: Helena
authors.initials: H
authors.lastname: Earl
authors.forename: Tim
authors.initials: T
authors.lastname: Perren
authors.forename: Martin
authors.initials: M
authors.lastname: Gore
authors.forename: Mojca
authors.initials: M
authors.lastname: Persic
authors.forename: Malcolm
authors.initials: M
authors.lastname: Adams
authors.forename: Lindsay
authors.initials: L
authors.lastname: James
authors.forename: Graham
authors.initials: G
authors.lastname: Temple
authors.forename: Michael
authors.initials: M
authors.lastname: Merger
authors.forename: Gordon
authors.initials: G
authors.lastname: Rustin
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D060046:Maintenance Chemotherapy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000098:blood supply / Q000188:drug therapy* / Q000201:enzymology; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000201:enzymology; D010919:Placebos; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D010919:Placebos; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; C530716:nintedanib