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
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 defined 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
Closed to recruitment - In Follow up
Population
Metastatic castration resistant prostate cancer (mCRPC) patients suitable to receive palliative docetaxel chemotherapy
Phase I: 3-18 patients
Phase II: 132 (66 per arm)
Contact Details
All trial enquiries should be sent to ctu@soton.ac.uk
Publications
Overall Survival Update for Patients with Metastatic Castration-resistant Prostate Cancer Treated with Capivasertib and Docetaxel in the Phase 2 ProCAID Clinical Trial - Simon Crabb, Gareth Griffiths, Denise Dunkley, Nichola Downs, et al.
Other Media
Results publicaton on SCTU website
Results publication in Southern Daily Echo
Funder
This trial was funded by Cancer Research UK (award reference no. C9317/A16029) with additional financial support from AstraZeneca UK Ltd.