AZD8835 in patients with advanced cancer
Research type
Research Study
Full title
A Phase I, Open-Label, Multicentre Dose-Escalation Study to Investigate the Safety and Pharmacokinetics of AZD8835 in Patients with Advanced Solid Tumours
IRAS ID
164702
Contact name
Hendrik-Tobias Arkenau
Contact email
Sponsor organisation
AstraZeneca AB
Eudract number
2014-003499-21
Duration of Study in the UK
2 years, 0 months, 31 days
Research summary
In this first-time-in-man study, AZD8835 will initially be administered as a single agent to patients with advanced solid malignancies. Patients will be treated at a starting dose of 20 mg twice daily (BID), administered weekly on Days 1 and 4 and will be escalated to reach a maximum-tolerated dose (MTD) in patients as defined by dose-limiting toxicities (DLTs). A BID intermittent dosing schedule administered weekly on Days 1 and 4 of an oral formulation of AZD8835 will be used, as deemed optimal and effective in non-clinical studies, primarily to determine the safety and tolerability of AZD8835. The pharmacokinetics (PK) of AZD8835 and potential biological activity will also be investigated.
In Part A of this study, AZD8835 will be administered as a single agent in an ascending dose escalation phase to investigate the appropriate monotherapy dose level for clinical use.
Following the single-agent dose-escalation phase of the study, additional patients with tumours that have documented mutations in the PIK3CA gene will be enrolled to a single-agent dose-expansion phase at the MTD or recommended Phase II dose (RP2D) (as appropriate) to explore safety, tolerability, PK, and biological activity at the selected dose (Part B).
In addition, a further dose-escalation phase will be initiated following the observation of specific pre-determined criteria in the single-agent dose escalation, in which postmenopausal patients with oestrogen receptor positive (ER+), HER2 negative breast cancer will receive AZD8835 with fulvestrant (Part C). The combination dose-escalation phase will investigate the appropriate combination dose level for clinical use.
Following the combination dose-escalation phase of the study, additional postmenopausal patients with ER+ breast cancer and tumours with documented mutations of the PIK3CA gene will be enrolled to a AZD8835 and fulvestrant combination dose-expansion phase at the MTD or RP2D (as appropriate) to explore the safety, tolerability, PK, and biological activity at the selected dose (Part D).
REC name
London - Chelsea Research Ethics Committee
REC reference
14/LO/2020
Date of REC Opinion
11 Dec 2014
REC opinion
Further Information Favourable Opinion