Dual REctal Angiogenesis or MEK inhibition radioTHERAPY trial

• Research type

  Research Study

• Full title

  Dual Phase I studies to determine the dose of Cediranib (AZD2171) or AZD6244 to use with conventional rectal chemoradiotherapy

• IRAS ID

  35574

• Contact name

  Mark Saunders

• Sponsor organisation

  The Christie NHS Foundation Trust

• Eudract number

  2009-016524-31

• Research summary

  Rectal cancer affects 10,000 new patients and causes 4,700 deaths each year in England and Wales. Historically, patients treated with surgery alone have a high risk of local recurrence. Clinical trials have established that local recurrence of operable rectal cancer can be reduced by treating patients with pre-operative pelvic radiotherapy and concurrent fluoropyrimidine-based (5-FU, capecitabine) chemotherapy, and this is now considered the standard treatment for this patient group. However, the best curative resection rates reported with this standard chemoradiotherapy treatment are approximately 50-60% and the generally accepted pathological complete response rates are only 15-20%. Therefore, there is considerable room for improvement and this trial aims to explore the potential of combining biological agents (Cediranib or AZD6244) with standard chemoradiotherapy. Cediranib is a potent Vascular Endothelial Growth Factor (VEGF) inhibitor, licensed for development by AstraZeneca Pharmaceuticals, which is expected to inhibit angiogenesis and, as a consequence, constrain tumour growth. AZD6244 is a potent, selective, uncompetitive inhibitor of MEK, licensed for development by AstraZeneca Pharmaceuticals, which is expected to impact tumour proliferation, differentiation and survival. This trial will determine the Maximum Tolerated Dose (MTD) and safety profile of Cediranib or AZD6244 when used in combination with standard chemoradiotherapy to take forward into phase II trials. Ultimately, the dose recommended for clinical practice will be determined by the MTD and also by the biological activity, which can be assessed by biomarkers and specialised imaging techniques. Therefore, this trial also includes the collection of a number of tissue and blood samples which will be tested for a range of biomarkers. In addition, 5 patients in the expanded cohort (i.e. when the MTD has been established) for AZD6244 and 5 patients in the expanded cohort for Cediranib will undergo DCE-MRI scans at 3 time points (baseline, after 10 days of dosing with AZD6244/Cediranib and after 5 weeks of chemoradiotherapy). The same 5 patients in the AZD6244 expanded cohort will also undergo FLT-PET imaging at the same time points as the DCE-MRI scans. The addition of the specialised biomarker testing and scanning techniques to this trial aims to obtain greater insight into the optimal biological dose and the response, resistance or toxicities for further evaluation at phase II.

• REC name

  North West - Greater Manchester Central Research Ethics Committee

• REC reference

  09/H1008/136

• Date of REC Opinion

  11 Mar 2010

• REC opinion

  Further Information Favourable Opinion