Saracatinib (AZD0530) and docetaxel in metastatic castrate-refactory prostate cancer

INTERVENTION: All patients will receive docetaxel by intravenous (iv) infusion once every 3 weeks for a maximum of 10 cycles with prednisolone 5mg twice daily by mouth from the first day of docetaxel up to at least day 21 of the final dose. Phase I Patients in the phase I component of the study will commence once‐daily saracatinib (AZD0530) on day 11 of the first cycle of docetaxel (dose as specified). They will continue until disease progression is confirmed. Phase II Patients in the phase II component of the study will be randomly assigned to receive either saracatinib (AZD0530) once daily by mouth at a dose to be defined in phase I or a matching placebo. This will be taken by mouth starting 7 days prior to the first dose of docetaxel and stopping when disease progression is confirmed. CONDITION: Prostate cancer ; Cancer ; Malignant neoplasm of prostate PRIMARY OUTCOME: 1. Phase I: To establish a safe and tolerable dose for saracatinib (AZD0530) given in combination with with docetaxel and prednisolone; 2. Phase II: To establish whether the efficacy of the combination of saracatinib (AZD0530) with docetaxel and prednisolone merits further study in patients with metastatic castrate‐refactory prostate cancer (mCRPC) SECONDARY OUTCOME: 1. Phase I: To investigate the effects of saracatinib (AZD0530) on docetaxel pharmacokinetics; 2. Phase II: To estimate the effect of saracatinib (AZD0530) on bone pain in patients with mCRPC INCLUSION CRITERIA: 1. Male aged 18 or over 2. Histologically or cytologically proven adenocarcinoma of the prostate with previously documented metastases 3. Proven disease progression since last change in therapy defined by at least one of the following: 3.1. Prostate‐specific antigen (PSA) progression as defined by the prostate cancer working group (PCWG2) criteria. This must be based on a series of at least three readings at least 7 days apart. The third reading must be greater than or equal to 2ng/ml. In the event where an intermediate reading is lower than a previous reading, then the patient will still be eligible (ie. the 3 readings do not need to be consecutive). The first of the three readings must have been obtained after commencing the previous systemic therapy, or, in the case of androgen receptor antagonists, after discontinuing. 3.2. Radiographic progression as defined by Response Evaluation Criteria In Solid Tumors (RECIST) for non‐bone disease 3.3. The ap