FGFR

• Research type

  Research Study

• Full title

  Proof-of-concept study of AZD 4547 in patients with FGFR1 or FGFR2 amplified tumours

• IRAS ID

  85968

• Contact name

  David Cunningham

• Sponsor organisation

  Royal Marsden Hospital NHS Foundation Trust

• Eudract number

  2011-003718-18

• ISRCTN Number

  n/a

• Clinicaltrials.gov Identifier

  n/a

• Research summary

  Background: Lung, breast and upper gastrointestinal cancers represent a significant global problem, resulting in over 2.5 million deaths per year worldwide. There is an unmet need for more efficacious therapies to improve outcomes, with the outlook for advanced lung and upper gastrointestinal cancers being particularly dismal. Recently, genetic modifications of the fibroblast growth factor receptor (FGFR) have been identified in a range of tumour types including breast, gastric and lung cancer. Pre-clinical data indicate that the resulting dysregulation of the FGFR signalling pathway is susceptible to attenuation by FGFR inhibitors, with potent growth inhibition seen in preclinical models of FGFR1/FGFR2 amplified tumours. AZD4547 is a novel potent and selective inhibitor of FGFR-1, 2 and 3 receptor tyrosine kinases, which has demonstrated activity in preclinical studies in FGFR amplified tumours. This is an open label, non-randomised, multi-centre study to assess the correlation between the anti-tumour efficacy of AZD4547 monotherapy and resulting molecular changes in paired biopsies in patients with previously treated FGFR amplified tumours. The 3 parallel groups will include patients as follows?½ Group 1 Advanced breast cancer with FGFR1 or FGFR2 gene amplification ?½ Group 2 Advanced gastro-oesophageal cancer with FGFR2 gene amplification. ?½ Group 3 Advanced squamous cell lung cancer with FGFR1 amplification. 16 patients will be recruited per tumour group and serial biopsies will be done at baseline and day 10-14 of treatment to assess molecular changes in response to treatment with AZD4547. CT scans will be done regularly to assess response to treatment. The results from this study will not only provide data on anti-tumour efficacy of AZD4547 and its correlation with molecular changes on treatment in FGFR amplified advanced cancers but may also provide valuable information regarding the molecular predictors of response and resistance to this novel agent.

• REC name

  London - City & East Research Ethics Committee

• REC reference

  11/LO/1595

• Date of REC Opinion

  9 Feb 2012

• REC opinion

  Further Information Favourable Opinion