NCT01160926

Dual REctcal Angiogenesis or MEK Inhibition radioTHERAPY Trial

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

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: The Christie NHS Foundation Trust · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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

Conditions

• Rectal Cancer

Interventions

Type	Name	Description
DRUG	AZD6244	Dose finding trial AZD6244 cohort 1 - 50mg bd AZD6244 cohort 2 - 75mg bd Capsule form, given for 10 days as single agent then for 35 days in combination with standard chemoradiotherapy
DRUG	Cediranib (AZD2171)	10 days single agent dosing with Cediranib then 35 days in combination with standard chemoradiotherapy AZD2171 cohort 1 - 15mg od AZD2171 cohort 2 - 20mg od AZD2171 cohort 3 - 30mg od Oral tablets

Timeline

• Start date: 2010-07-01
• Primary completion: 2013-10-01
• Completion: 2016-11-04
• First posted: 2010-07-13
• Last updated: 2023-04-24

Locations

1 site across 1 country: United Kingdom