A Study of Enzalutamide in Combination With AZD5363 in Patients With mCRPC (RE-AKT)

A multicentre prospective, randomised, phase II interventional study in mCRPC patients previously treated with 1?2 lines of chemotherapy and at least 12 weeks of abiraterone with a safety run?in and single stage phase II expansion cohort.

Primary Outcome Measures:

• Phase I: Type, frequency, severity, seriousness and relatedness of adverse events [ Time Frame: 35 days ]
  • Type according to Medical Dictionary for Regulatory Activities (MedDRA), frequency according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4, seriousness, and relatedness of study treatment-emergent adverse events will be assessed
• Phase I: Laboratory abnormalities will be assessed according to NCI CTCAE v4 [ Time Frame: 35 days ]
• Randomised phase II: Best overall tumour response [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to an estimated 22-24 months ]
  • Best overall tumour response as defined by Prostate Specific Antigen (PSA) decline of ≥50% (according to PCWG2), confirmed objective response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 or ONLY for patients with detectable circulating tumour cell count of ≥5/7.5ml blood at baseline, conversion of CTC <5/7.5ml blood nadir
• Phase II expansion: Best overall tumour response [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to an estimated 22-24 months ]
  • Best overall tumour response as defined by PSA decline of ≥50% (according to PCWG2), confirmed objective response by RECIST 1.1 or ONLY for patients with detectable circulating tumour cell count of ≥5/7.5ml blood at baseline, conversion of CTC <5/7.5ml blood nadir

Secondary Outcome Measures:

• Phase I and phase II expansion only - Pharmacokinetic (PK) assay analyses [ Time Frame: 35 days ]
  • PK assay analysis including endpoints of Peak Plasma Concentration (Cmax) and Area under the plasma concentration versus time curve (AUC)
• Phase I - Antitumour activity of the combination [ Time Frame: 35 days ]
• Randomised phase II and phase II expansion - Overall survival and radiographic progression free survival [ Time Frame: From date of randomization/trial entry until the date of first documented progression or date of death from any cause, whichever came first, assessed up to (estimated) 12 months ]
• Maximum PSA decline and circulating tumour cell (CTC) fall [ Time Frame: 12 weeks ]
  • Maximum PSA decline and CTC fall by 30% at any time during the trial and at 12 weeks.
• Pain Palliation - Randomised phase II only [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to (estimated) 12 months ]
  • Pain palliation will be assessed using the Brief Pain Inventory (Short Form) (BPI-SF) worst pain intensity score
• Number of Adverse events will be graded according to NCI-CTCAE v4 [ Time Frame: From trial entry until 30 days post date of last dose or death from any cause ]