Dual REctcal Angiogenesis or MEK Inhibition radioTHERAPY Trial — DREAMtherapy  

Rectal Cancer Clinical Trial

Official title: Dual Phase I Studies to Determine the Dose of Cediranib (AZD2171) or AZD6244 to Use With Conventional Rectal Chemoradiotherapy

Status Terminated

Clinical Trial Summary

To determine the maximum tolerated dose (MTD) of AZD6244 or AZD2171 when combined with pre-operative capecitabine and radiotherapy in patients with locally advanced rectal cancer.

Clinical Trial Description

The best curative resection rates reported for patients with operable rectal cancer treated with standard chemoradiotherapy are approximately 50-60%.The pathological complete response rates are only 10-20%. Therefore, there is a need for more effective treatment. In this trial we will evaluate the combination of chemoradiotherapy with either a VEGFR (vascular endothelial growth factor receptor) or MEK (MAP Kinase)inhibitor.

Aims

1. Define the tolerability, MTD (maximum tolerated dose) and DLT (dose limiting toxicities) of chemoradiotherapy in combination with

• cediranib, a VEGF receptor tyrosine kinase inhibitor that inhibits angiogenesis or

• AZD6244, a potent MEK inhibitor that inhibits cell proliferation

2. Define a dose suitable for phase II evaluation

3. Test the impact of the combination on soluble and imaging (FLT-PET and DCEMRI/DWI) biomarkers to guide their use in phase II testing Summary Patients will receive standard chemoradiotherapy plus ascending doses of AZD6244 or cediranib from day -10 (relative to start of chemoradiotherapy) to day 35. If feasible, patients' tumours will be resected 10-12 weeks after treatment. Translational studies on available tissue and blood will be performed and DCE-MRI/DWI and FLT-PET will be carried out on 5 patients in the expanded cohort for AZD6244 (FLT-PET and DCE-MRI) and 5 patients in the expanded cohort for cediranib (DCE-MRI).

Cohorts Cediranib - 15mg od, 20mg od and 30mg od AZD6244 - 50mg bd and 75mg bd ;

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

• NCT number: NCT01160926
• Study type: Interventional
• Source: The Christie NHS Foundation Trust
• Status: Terminated
• Phase: Phase 1
• Start date: July 2010
• Completion date: November 4, 2016