Title
An open label phase I/randomised, double blind phase II study in metastatic castration resistant Prostate Cancer of AZD5363 In combination with Docetaxel and prednisolone chemotherapy
Description
A phase I/II trial to determine if the addition of the AKT inhibitor AZD5363 to docetaxel and prednisolone (DP) prolongs progression free survival (PFS) in metastatic castration resistant prostate cancer (mCRPC) to a degree worthy of further investigation.
Objectives
Primary Endpoints:
Phase I:
- Determination of a suitable dose of AZD5363 using a 4 days on/3 days off continuous schedule, in combination with DP
Phase II:
- Progression free survival (PFS) in patients receiving AZD5363 versus placebo when combined with DP in mCRPC
Secondary Endpoints:
Phase I:
- Safety and tolerability profiles using CTCAE version 4.03
- AZD5363 pharmacokinetics in combination with DP
Phase II:
- Overall survival
- Bone pain changes using the brief pain inventory
- PFS excluding biochemical (PSA) alone progression
- Biochemical (PSA) response rates according to PCWG2 criteria
- Safety and tolerability profiles using CTCAE version 4.03
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Trial Design
ProCAID will first comprise a dose-finding, single arm, open label phase I study exploring the combination of AZD5363 and Docetaxel and prednisolone chemotherapy (DP). This will be followed by a double-blind, randomised phase II study comparing DP + AZD5363 with DP + placebo. All patients will have chemotherapy naive mCRPC and will be suitable for treatment with palliative docetaxel. Patients may, but are not required to, have had prior second generation anti-hormonal therapies (e.g., abiraterone, enzalutamide).
Phase I:
- AZD5363 at dose levels between 320 mg bd and 480 mg bd, taken 4 days on/3 days off, continuously starting from day 2 of cycle 1 of DP onwards.
Phase II:
- AZD5363 twice daily at a dose level Ìýdefined in phase I (experimental arm) or matching placebo (control arm), taken 4 days on/3 days off, continuously from day 2 of cycle 1 of DP onwards.
Trial Status
Complete
Population
Metastatic castration resistant prostate cancer (mCRPC) patients suitable to receive palliative docetaxel chemotherapy
Phase I:Ìý3-18 patients
Phase II:Ìý132 (66 per arm)
Contact Details
All trial enquiries should be sent to ctu@soton.ac.uk
Publications
- Simon Crabb, Gareth Griffiths, Denise Dunkley, Nichola Downs, et al.
- Simon Crabb, Gareth Griffiths, et al.
- Simon Crabb, Alison Birtle, et al.
Other Media
Results publicaton on SCTU website
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Funder
This trial was funded by Cancer Research UK (award reference no. C9317/A16029) with additional financial support from AstraZeneca UK Ltd.