GUIDE: This Phase II trial is trying to understand how effective chemotherapy (docetaxel) is when delivered intermittently, compared to continuously, in men with metastatic castration-resistant prostate cancerA Randomised Non-comparative Phase II Trial of Biomarker-driven Intermittent Docetaxel Versus Standard-of-care (SOC) Docetaxel in Metastatic Castration-resistant Prostate Cancer (mCRPC)

Inclusion

PRESCREENING INCLUSION CRITERIA

1. Patient has provided written informed consent using the GUIDE pre-screening PICF
2. Age ≥ 18 years at the time of pre-screening consent
3. Males with metastatic castration-resistant prostate cancer (as per PCWG3) AND are planned to commence docetaxel chemotherapy
4. WHO Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix 1)
5. Histological confirmation of prostate cancer

6. Patients must have adequate bone marrow and hepatic function within 14 days prior Cycle 1 day 1:

   • Haemoglobin ≥ 90 g/L independent of transfusions (no red blood cell transfusion in last 4 weeks)
   • Platelets ≥ 100 x 109/L
   • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
   • Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN)
   • Alanine aminotransferase (ALT)/Aspartate aminotransferase (AST) ≤ 2.5 x ULN
7. Willing and able to comply with all pre-screening study requirements, including blood tests for mGSTP1 analysis before and during docetaxel treatment

MAIN SCREENING INCLUSION CRITERIA

1. Patient has provided written informed consent for the main GUIDE study PICF
2. Patient has a detectable plasma mGSTP1 deoxyribonucleic acid (DNA) as measured by central laboratory at prescreening prior to commencing first cycle of docetaxel chemotherapy
3. Patient has commenced 3 cycles of docetaxel
4. Patient has undetectable plasma mGSTP1 DNA as measured by central laboratory from blood taken prior to the third cycle of docetaxel
5. Patient is willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.

Exclusion

PRESCREENING EXCLUSION CRITERIA

1. Prior docetaxel or cabazitaxel chemotherapy for castration-resistant prostate cancer
2. Prior docetaxel in the castration sensitive prostate cancer setting within the previous 2 years
3. Known hypersensitivity to docetaxel or its excipients
4. Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
5. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol

MAIN SCREENING EXCLUSION CRITERIA

1. Known hypersensitivity to docetaxel or its excipients
2. Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
3. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol
4. Progressive disease by RECIST 1.1 within the first 3 cycles of docetaxel