Utilising CTC Counts to Optimize Systemic Therapy of Metastatic Prostate Cancer

Inclusion Criteria: 1. Written informed consent. 2. Age ≥18 years 3. Histologically confirmed diagnosis of adenocarcinoma of the prostate with availability of archival tumour tissue for molecular analyses (small cell prostate cancer is an exclusion); if no histological diagnosis has ever been acquired a fresh bone marrow trephine tumour biopsy confirming the presence of CRPC must be pursued. o Tumour tissue blocks will be requested for processing. Sections will be cut with the blocks then returned to the referring hospital. If the block is not available, at least ten tumour tissue sections (formalin-fixed paraffin-embedded) at 5 microns each will be requested. 4. Metastatic castration-resistant disease with only bone metastases, confirmed by bone scan (within 4 weeks) or CT (within 6 weeks), of starting this trial (Cycle 1 Day 1). Patients with local recurrence, and bone metastases with an associated soft tissue component, will be allowed into the trial. Pelvic lymphadenopathy \<1.5cm in short axis is not an exclusion. 5. Systemic chemotherapy indicated for disease progression, defined as: o Bone Scan Progression: Two or more new documented bone lesions over previous 6 months. AND/OR o Increasing serum PSA level: Two consecutive increases in PSA levels documented over a previous reference value obtained at least one week apart are required. If the third PSA value is less than the second, an additional fourth test to confirm the rising PSA is required. 6. Baseline laboratory values as stated below: * Creatinine ≤1.5 x upper limit of normal (ULN) * Bilirubin ≤1.0 x ULN * SGOT (AST) and SGPT (ALT) ≤2.5x ULN * Castrate serum testosterone level (\<50 ng/dL-or-\<1.7 nmol/L) * ANC ≥1.5 x 109cells/L * Platelet count ≥100 x 109/L * PSA ≥ 5ng/mL 7. CTC levels ≥ 5 cells / 7.5 mL 8. Prior treatment with abiraterone and/or enzalutamide, discontinued due to disease progression. 9. Patient willing to continue primary androgen suppression with gonadotropin-releasing hormone (GnRH) analogues (either agonists or antagonists) throughout the study, unless treated with bilateral orchiectomy. 10. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (see Appendix A2). 11. At least 3 weeks should have elapsed since stopping any investigational agent at the time of randomisation. More than 4 weeks since completion of radiotherapy, other than when a single palliative fraction is administered when only a two week interval is required before trial treatment commencement. 12. Patient recovered from any therapy-related toxicity to ≤ grade 2, (except alopecia, anaemia and any signs or symptoms of androgen deprivation therapy). 13. Patient willing to comply with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial 14. Participants must be surgically sterile or must agree to use effective contraception during the period of the therapy and for 12 months after the last dose of study treatment. Effective contraception is defined as double barrier contraception (e.g. condom plus spermicide in combination with a female condom, diaphragm, cervical cap or intrauterine device). Exclusion Criteria 1. Received any prior cytotoxic chemotherapy as treatment for castration-resistant prostate cancer. Patients that have received chemotherapy for hormone-sensitive metastatic prostate cancer will be allowed onto the trial, if the patient merits retreatment with docetaxel and at least 12 months has elapsed since the patient has completed that previous docetaxel therapy. 2. Measurable soft tissue or lymph node metastases or any metastatic disease outside the bone that is RECIST measurable will be an exclusion (unless it is pelvic nodal disease \<1.5cm in short axis). Bone metastases with associated soft tissue components will also not be an exclusion. 3. Received any cycling, intermittent or continuous hormonal treatment 28 days prior to randomisation with the exception of the continuous LHRH analogues. 4. History of or current documented brain metastasis or carcinomatous meningitis, treated or untreated. Brain imaging for asymptomatic patients is not required. 5. Current symptomatic cord compression requiring surgery or radiation therapy. (Once the patient is successfully treated the patient will be considered eligible for the study). 6. Active second malignancy (except non-melanoma skin or superficial bladder cancer) defined as requiring anticancer therapy or within the previous two years. 7. Serious medical conditions such as heart failure, myocardial infarction, pulmonary thromboembolism within 12 months; stroke or treatment of a major active infection within 3 months of randomisation, as well as any significant medical illness that in the opinion of the Investigator would preclude protocol therapy. 8. Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device. Concomitant participation in observational studies is acceptable. 9. Hypersensitivity to the active substance, to any of its excipients (including polysorbate 80) or to other taxanes. 10. Concomitant vaccination with yellow fever vaccine 11. Concomitant use of medicinal products that are strong CYP3A inducers