Phase II trial of cediranib +/- gefitinib for recurrent glioblastoma

• Research type

  Research Study

• Full title

  Multi-centre, randomised, double-blind phase II study comparing cediranib (AZD2171) plus gefitinib (Iressa, ZD1839) with cediranib plus placebo in subjects with recurrent/progressive glioblastoma (DORIC Trial)

• IRAS ID

  68160

• Contact name

  Paul Mulholland

• Sponsor organisation

  Joint UCLH and UCL Biomedical Research Unit

• Eudract number

  2010-021531-13

• ISRCTN Number

  n/a

• Research summary

  BackgroundNo standard treatment exists for recurrent glioblastoma and prognosis is poor.Glioblastoma is a highly vascular tumour and is associated with high levels of vascular endothelial growth factor (VEGF). Epidermal growth factor receptor (EGFR) is commonly amplified and/or mutated in glioblastoma. In this study we propose the use of a combination of therapies, targeting VEGF receptor (cediranib; AZD2171) and EGFR (gefitinib; Iressa; ZD1839) pathways in recurrent glioblastoma.A phase II study of cediranib in subjects with relapsed glioblastoma demonstrated promising results. A randomised, phase III study (REGAL) comparing cediranib alone against cedirianib plus lomustine or lomustine alone has shown that the anti-tumour effect of cediranib is at least equivalent to lomustine. A phase I study combining cediranib with gefitinib has shown this combination to be safe.Specific aims of the researchTo determine the progression free survival, overall survival, radiological response, and safety and tolerability of cediranib in combination with gefitinib versus cediranib (plus placebo). Potential biomarker roles of EGFR vIII, PTEN, methylation of MGMT, IDH 1 and 2 will be assessed.Summary of the studyPatients with recurrent/progressive glioblastoma will be randomised (1:1) to receive cediranib in combination with gefitinib or cediranib plus placebo. Patients will be reviewed weekly for the first 6 weeks and 3 weekly thereafter and will undergo MRI assessment at base-line and at 6-week intervals. The recruitment target is 112 patients, and recruitment is expected to take ~18 months.

• REC name

  London - Harrow Research Ethics Committee

• REC reference

  10/H0715/77

• Date of REC Opinion

  17 Feb 2011

• REC opinion

  Further Information Favourable Opinion