NCT01668550

A Phase I Study of AZD0424 Alone and in Combination in Advanced Solid Tumours

A Cancer Research UK Phase I Study to Determine the Maximum Tolerated Dose of the Oral Src/Abl Inhibitor AZD0424, and to Identify Tolerable and Effective AZD0424 Combination Regimens for the Treatment of Advanced Solid Tumours

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 43 (actual)
• Sponsor: Cancer Research UK · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine the maximum tolerated dose of the oral Src/Abl inhibitor AZD0424, and to find tolerable and effective AZD0424 combination regimens for the treatment of advanced solid tumours

Detailed description

AZD0424 is a potent orally available, potent (IC50 approximately 4 nM) inhibitor of Src and ABL1 kinases with additional activity against Src family kinase (SFK) members including Yes and Lck. AZD0424 was selective for SFKs and ABL1 kinase over C-terminal Src kinase (a negative regulator of Src) and a range of other kinase targets. The anti-cancer activity of AZD0424 is thought to be mediated primarily by anti-migratory and anti-invasive signalling and, as such, it is expected that in the late stage cancer setting strong signals of efficacy with this compound used as a single agent are unlikely, requiring it to be administered in combination with other anti-cancer agents. In summary the study will be performed in four main stages: * AZD0424 monotherapy, dose escalation: Phase Ia single agent (AZD0424) dose escalation study to determine the MTD. * AZD0424 monotherapy, dose expansion: Phase Ib single agent dose expansion at MTD (up to six additional patients may be recruited in order to provide paired tumour biopsies for PD analysis). * Combination arm dose escalation: Provided that it is deemed appropriate (after review of available clinical data from the monotherapy part of the trial, and available preclinical and published data on the combination), a Phase Ia dose escalation arm of AZD0424 in combination with the selected agent will proceed to determine the MTD for the combination and a recommended Phase II dose. * Combination arm dose expansion: Phase Ib combination arm using the recommended Phase II dose for both AZD0424 and the combination agent.

Conditions

• Advanced Solid Tumours

Interventions

Type	Name	Description
DRUG	AZD0424	AZD0424 will be administered as a flat dose orally once a day. One treatment cycle consists of 28 days of continuous drug administration with AZD0424, with the flexibility to introduce treatment breaks if required due to cumulative toxicity. Combination agents and treatment regimen with AZD0424 will be confirmed and approved at a later date.

Timeline

• Start date: 2012-10-01
• Primary completion: 2016-05-01
• Completion: 2016-05-01
• First posted: 2012-08-20
• Last updated: 2018-02-05

Locations

3 sites across 1 country: United Kingdom