Metastatic prostate cancer Cancer
Conditions
Interventions
Docetaxel 75mg/m2 IV infusion every 21 days for 6 cycles
Sponsors
University Hospital Southampton NHS Foundation Trust
Eligibility
Sex/Gender
Male
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Diagnosis of metastatic prostate cancer 2. Histological confirmation of prostate adenocarcinoma with an archival prostate cancer tumour sample available and transferred for central translational analysis prior to randomisation. Patients will be viewed as eligible if a suitable sample is received centrally and analysed. If a Decipher Prostate score or PTEN Inactivity Score cannot be determined for technical reasons, the patient may still be entered and randomised into the trial. 3. Have an initial PSA level, prior to commencing ADT (including any bicalutamide or other AR antagonist run in if used for tumour ‘flare’ prophylaxis), of =2 ng/ml 4. PSA never <0.2 ng/ml since starting hormonal therapy, including a screening PSA level taken within 28 days of randomisation (if more than one PSA level is taken during the 28 days before randomisation, then all must meet this criteria point) 5. Within 5 to 8 months from the first dose of ADT given for mHSPC (or the date of surgical castration) to the date of randomisation. This timing requirement does not indicate from first dose of bicalutamide or other agent for tumour ‘flare’ cover. Any conventional approach to ADT is acceptable including LHRH antagonists, LHRH agonists, oestradiol patches and surgical castration. If a patient has received prior adjuvant ADT, or other hormonal therapy, they remain eligible if a minimum of 12 months had elapsed between completing adjuvant hormonal therapy and then commencing ADT for mHSPC if there has been documented PSA progression and testosterone recovery (a level above the lower level of normal for the treating institution) in between 6. A minimum of 12 weeks from the commencement of ARPI to the date of randomisation. Abiraterone acetate, enzalutamide, and darolutamide are all acceptable forms of ARPI. Patients may have had ARPI pauses, or switched from one ARPI to another, if this was for reasons of tolerability, toxicity management or to permit trial eligibility (i.e. switching from apalutamide to an alternative), according to local institutional practice, and with the intention of continuing ARPI treatment whilst still in the hormone sensitive setting. 7. Serum testosterone =1.7 nmol/L 8. ECOG performance status 0 to 2 9. Adequate clinical, haematological and biochemical parameters to receive docetaxel chemotherapy if allocated, and all relevant supportive medications, and ongoing ADT + ARPI, according to local institutional guidelines and investigator judgement. This must include (within 4 weeks of randomisation): 9.1. Neutrophil count =1.5 x 10e9/L 9.2. Platelet count =100 x 10e9/L 9.3. Haemoglobin =90 g/dL 9.4. Total bilirubin =upper limit of normal (ULN), unless the patient has Gilbert’s syndrome 9.5. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) =1.5 x ULN. Patients may have either or both undertaken according to local institutional practice (if both are done during screening then both should satisfy this criterion point) 10. Age =18 years 11. Life expectancy anticipated =3 months 12. Able to provide written informed consent
Exclusion criteria
Exclusion criteria: 1. Prostate cancer progression to castration resistance as defined and determined by the treating institutional clinical, biochemical (PSA) and/or radiological standards for assessment 2. Active malignancy other than prostate cancer, non-melanomatous skin cancer or non-muscle invasive bladder cancer. A prior cancer diagnosis, where active treatment was discontinued 2 years, or more, prior to randomisation is permitted 3. Previous or current chemotherapy, therapeutic radionuclide, PARP inhibitor or AKT inhibitor treatment for prostate cancer 4. Hypersensitivity to docetaxel or excipients 5. Any serious or unstable medical illness or condition that, in the view of the investigator, could impair the safety of the participant and/or interfere with their compliance with the study procedures, their ongoing use of ADT + ARPI or the use of docetaxel chemotherapy 6. Patients with a partner of child-bearing potential who are not using a highly effective method of contraception, who are unwilling to use condoms during and for 4 months after the last dose of docetaxel
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival (OS) defined as the time (in days) from date of randomisation until date of death from any cause: 1. In all patients 2. In a subgroup with Decipher Prostate classifier High cancers | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. PSA PFS defined as the time (in days) from date of randomisation until the earliest date of PSA progression defined in accordance with PCWG3 (a =25% increase in PSA and an absolute increase of =2 ng/ml, from the PSA nadir and confirmed by a second value =3 weeks later) or death from any cause 2. cPFS (clinical PFS) defined as the time from randomisation to date of radiographic progression, PSA progression, initiation of new prostate cancer treatment or death, whichever occurs first. | — |
Countries
England, United Kingdom
Contacts
Public ContactINTENSIFY Team
Outcome results
None listed