title: An open-label, phase 2 study evaluating the efficacy and safety of the anti-IGF-1R antibody cixutumumab in patients with previously treated advanced or metastatic soft-tissue sarcoma or Ewing family of tumours.
abstract: BACKGROUND
  Cixutumumab (IMC-A12), a fully human immunoglobulin G1 (IgG1) monoclonal antibody, exerts preclinical activity in several sarcoma models and may be effective for the treatment of these tumours.
  
  
  METHODS
  In this open-label, multicentre, phase 2 study, patients with previously treated advanced or metastatic rhabdomyosarcoma, leiomyosarcoma, adipocytic sarcoma, synovial sarcoma or Ewing family of tumours received intravenous cixutumumab (10mg/kg) for 1h every other week until disease progression or discontinuation. The primary end-point was the progression-free survival rate (PFR), defined as stable disease or better at 12 weeks. In each tier of disease histology, Simon's optimum 2-stage design was applied (PFR at 12 weeks P0=20%, P1=40%, α=0.10, β=0.10). Stage 1 enrolled 17 patients in each disease group/tier, with at least four patients with stable disease or better required at 12 weeks to proceed to stage 2.
  
  
  RESULTS
  A total of 113 patients were enrolled; all tiers except adipocytic sarcoma were closed after stage 1 due to futility. The 12-week PFR was 12% for rhabdomyosarcoma (n=17), 14% for leiomyosarcoma (n=22), 32% for adipocytic sarcoma (n=37), 18% for synovial sarcoma (n=17) and 11% for Ewing family of tumours (n=18). Median progression-free survival (weeks) was 6.1 for rhabdomyosarcoma, 6.0 for leiomyosarcoma, 12.1 for adipocytic sarcoma, 6.4 for synovial sarcoma and 6.4 for Ewing family of tumours. Among all patients, the most frequent treatment-emergent adverse events (AEs) were nausea (26%), fatigue (23%), diarrhoea (23%) and hyperglycaemia (20%).
  
  
  CONCLUSIONS
  Patients with adipocytic sarcoma may benefit from treatment with cixutumumab. Cixutumumab treatment was well tolerated, with limited gastrointestinal AEs, fatigue and hyperglycaemia.
authors.affiliation: University Hospitals Leuven, KU Leuven, Leuven, Belgium. Electronic address: patrick.schoffski@uzleuven.be.
authors.forename: P
authors.initials: P
authors.lastname: Schöffski
authors.forename: D
authors.initials: D
authors.lastname: Adkins
authors.forename: J-Y
authors.initials: JY
authors.lastname: Blay
authors.forename: T
authors.initials: T
authors.lastname: Gil
authors.forename: A D
authors.initials: AD
authors.lastname: Elias
authors.forename: P
authors.initials: P
authors.lastname: Rutkowski
authors.forename: G K
authors.initials: GK
authors.lastname: Pennock
authors.forename: H
authors.initials: H
authors.lastname: Youssoufian
authors.forename: H
authors.initials: H
authors.lastname: Gelderblom
authors.forename: R
authors.initials: R
authors.lastname: Willey
authors.forename: D O
authors.initials: DO
authors.lastname: Grebennik
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012509:Sarcoma / Q000188:drug therapy*; D012512:Sarcoma, Ewing / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C557414:cixutumumab
keywords: Adipocytic sarcoma; Cixutumumab; Ewing family of tumours; Insulin-like growth factor receptor; Leiomyosarcoma; Rhabdomyosarcoma; Soft-tissue sarcoma; Synovial sarcoma