Prostate cancer Cancer Malignant neoplasm of prostate
Conditions
Interventions
Patients with a Circulating Tumour Cell (CTC) count of over (and including) 5 cells at screening will be randomised 1:1 to either the control group (standard of care) or intervention group (CTC guided
needs to be subsequently confirmed by CTC progression on Cycle 3 Day 1 CTC count).If a patient is found to have two successive
Sponsors
The Institute of Cancer Research
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Written informed consent 2. Male patients over and including 18 years on the date of consent 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 tumour biopsy confirming the presence of CRPC must be pursued 4. Metastatic castration-resistant disease with only bone metastases, confirmed by bone scan (within 4 weeks) or CT/ whole body MRI (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 <2cm in size is not an exclusion. 5. Systemic chemotherapy indicated for disease progression, defined as: 5.1. Bone Scan Progression: Two or more documented new bone lesions over previous 6 months AND/OR 5.2. 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: 6.1. Creatinine =1.5 x upper limit of normal (ULN) 6.2. Bilirubin =1.0 x ULN 6.3. SGOT (AST) and SGPT (ALT) =2.5 x ULN 6.4. Castrate serum testosterone level (<50 ng/dL-or-<1.7 nmol/L) 6.5. ANC =1.5 x 109cells/L 6.6. Platelet count =100 x 109/L 6.7. 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) 0-2 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 has recovered from any therapy-related toxicity to = grade 2, (except alopecia, anaemia and any signs or symptoms of androgen deprivation therapy) 13. Patients willing to comply with the study protocol and follow-up schedule; these conditions should be discussed with the patient before registration in the trial 14. Patients 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
Exclusion criteria
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 <2cm in size). 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival is measured by the time from randomisation date to the date of death or last follow-up of the patient. After on-treatment visits, patient status and survival of patient are assessed every 12 weeks (patients’ notes and/or interview) until death or loss to follow of the patient, or end of study. The time point of interest for the main analysis is the estimate of overall survival at 24 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Proportion of patients in the intervention group that undergo a chemotherapy switch guided by CTC results. This is assessed once 200 patients are recruited and have completed at least 24 weeks of docetaxel treatment 2. Number of cycles of docetaxel administered per patient (with a maximum of 10 cycles allowed) reviewed at 24 months post last patient first visit. 3. Safety is assessed by the rate of adverse events with first and second line chemotherapy; these are assessed at baseline, CxD1 for both treatments, Pre-cabazitaxel follow up visits (if patient receives 10 cycles of docetaxel), EOT and First Off Treatment Follow Up Visit 4. Quality of life is assessed using the FACT-P and EQ-5D questionnaires at baseline, CxD1 for both treatments, Pre-cabazitaxel follow up visits (if patient receives 10 cycles of docetaxel), EOT and First Off Treatment Follow Up Visit 5. Pain (progression and response) is measured by the Brief Pain Inventory Form and the Analgesic use at CxD1 for both treatments 6. Progression Free Survival is measured by the time from randomisation until disease progression, death or end of follow-up, whatever occurs first. Disease progression is defined per the PCWG2 criteria and includes: PSA progression, radiographic progression and clinical progression 6.1. PSA progression is assessed at baseline, CxD1 for both treatments, Pre-cabazitaxel follow up visits (if patient receives 10 cycles of docetaxel), EOT and First Off Treatment Follow Up Visit 6.2. Radiographic progression is assessed by CT/whole Body MRI and bone scans performed at baseline and as per clinical practice, every 2-3 months 6.3. Clinical progression is assessed by pain, analgesic use, patient reported symptoms and clinical assessment and is assessed at baseline and CxD1 for both treatments, Pre-cabazitaxel follow up visits (if patient receives 10 cycles of do | — |
Countries
United Kingdom
Contacts
Public ContactMarie Hyslop
Outcome results
None listed