PMID- 23835252
OWN - NLM
STAT- MEDLINE
DCOM- 20140506
LR  - 20191210
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 49
IP  - 15
DP  - 2013 Oct
TI  - 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.
PG  - 3219-28
LID - S0959-8049(13)00485-1 [pii]
LID - 10.1016/j.ejca.2013.06.010 [doi]
AB  - 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%, alpha=0.10, beta=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.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Schoffski, P
AU  - Schoffski P
AD  - University Hospitals Leuven, KU Leuven, Leuven, Belgium. Electronic address: 
      patrick.schoffski@uzleuven.be.
FAU - Adkins, D
AU  - Adkins D
FAU - Blay, J-Y
AU  - Blay JY
FAU - Gil, T
AU  - Gil T
FAU - Elias, A D
AU  - Elias AD
FAU - Rutkowski, P
AU  - Rutkowski P
FAU - Pennock, G K
AU  - Pennock GK
FAU - Youssoufian, H
AU  - Youssoufian H
FAU - Gelderblom, H
AU  - Gelderblom H
FAU - Willey, R
AU  - Willey R
FAU - Grebennik, D O
AU  - Grebennik DO
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20130705
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 2285XW22DR (cixutumumab)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal/adverse effects/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Sarcoma/*drug therapy
MH  - Sarcoma, Ewing/*drug therapy
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - Adipocytic sarcoma
OT  - Cixutumumab
OT  - Ewing family of tumours
OT  - Insulin-like growth factor receptor
OT  - Leiomyosarcoma
OT  - Rhabdomyosarcoma
OT  - Soft-tissue sarcoma
OT  - Synovial sarcoma
EDAT- 2013/07/10 06:00
MHDA- 2014/05/07 06:00
CRDT- 2013/07/10 06:00
PHST- 2013/04/11 00:00 [received]
PHST- 2013/06/06 00:00 [revised]
PHST- 2013/06/10 00:00 [accepted]
PHST- 2013/07/10 06:00 [entrez]
PHST- 2013/07/10 06:00 [pubmed]
PHST- 2014/05/07 06:00 [medline]
AID - S0959-8049(13)00485-1 [pii]
AID - 10.1016/j.ejca.2013.06.010 [doi]
PST - ppublish
SO  - Eur J Cancer. 2013 Oct;49(15):3219-28. doi: 10.1016/j.ejca.2013.06.010. Epub 2013 
      Jul 5.