Castration-resistant Prostate Cancer, Chemotherapy, Circulating Tumor Cells, Prostate Carcinoma
Conditions
Keywords
Docetaxel, Cabazitaxel
Brief summary
This study compares the biological activity of cabazitaxel (6 cycles) to that of docetaxel (6 cycles) in metastatic castrate-resistant prostate cancer (mCRPC) patients with docetaxel resistant mCRPC defined as ≥5 circulating tumor cells (CTCs) / 7.5 mL after 2 cycles of docetaxel. Patients with docetaxel resistant metastatic castration-resistant prostate cancer (mCRPC) based on circulating tumor cell (CTC) enumeration (patients with ≥5 CTCs / 7.5 mL before docetaxel chemotherapy and after 2 cycles of docetaxel) will receive either 6 additional cycles of docetaxel or 6 additional cycles of cabazitaxel after randomisation. A cohort of patients with docetaxel sensitive metastatic castration-resistant prostate cancer (mCRPC) based on circulating tumor cell (CTC) enumeration (patients ≥5 CTCs / 7.5 mL before docetaxel chemotherapy and \<5 CTCs / 7.5 mL after 2 cycles of docetaxel) will receive 6 additional cycles of docetaxel.
Interventions
DRUGCabazitaxel
Experimental treatment arm: patients will be treated with intravenous cabazitaxel 20 mg/m² every 3 weeks up to 10 cycles.
DRUGDocetaxel
standard treatment arm and cohort: Docetaxel is administered at the dose of 75 mg/m² over 1 hour every 3 weeks for 6 cycles (D1=D22).
Sponsors
National Cancer Institute, France
Institut du Cancer de Montpellier - Val d'Aurelle
Institut Bergonié
UNICANCER
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent signed prior any study-related procedures 2. Adult men ≥18 years 3. Histologically confirmed prostate adenocarcinoma 4. Metastatic disease as evidenced by imaging (bone scan, CT-scan, MRI and/or PET-choline). 5. Documented progressive disease while receiving continuous hormonal treatment with luteinizing hormone-releasing hormone (LH-RH) agonist or antagonist or after surgical castration (at least one visceral or soft tissue metastatic lesion, including a new lesion). Patient with non-measurable disease must have documented rising prostate-specific antigen (PSA) levels or appearance of new lesion 6. Effective castration assessed by testosterone levels ≤50 ng/dL 7. Patients with a Eastern Cooperative Oncology Group (ECOG) performance status ≤2 8. Patients affiliated to social security scheme
Exclusion criteria
1. Prior chemotherapy for metastatic prostate cancer except estramustine \<1 year from the end of adjuvant and/or neoadjuvant chemotherapy for localized disease \<1 year from the end of chemotherapy for de novo metastatic prostate cancer 2. Prior isotope therapy, whole pelvic radiotherapy or radiotherapy to \>30% of bone marrow 3. Less than 1 month elapsed from prior treatment with radiotherapy, surgery and less than 2 weeks from any previous hormonal treatment except for LH-RH agonists/antagonists (which are to be continued). Patients may be treated with bisphosphonates prior to study entry which should be pursued, 4. History of brain metastases, uncontrolled spinal cord compression, carcinomatous meningitis or new evidence of brain or leptomeningeal disease 5. Patient with any of the following abnormal laboratory tests: hemoglobin \<10 g/dL, absolute neutrophil count \<1.5 x 10⁹/L, platelets \<100 x 10⁹/L, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \>1.5 x upper limit of normal (ULN), total bilirubin \>1.0 ULN, creatinine clearance \<40 ml/mn (MDRD) 6. History of hypersensitivity to polysorbate 80 or docetaxel 7. Contraindication to the use of corticosteroids 8. Peripheral neuropathy grade ≥2 according to NCI CTCAE v4.0 9. Ventricular ejection fraction \<50% (echography or scintigraphy) 10. Any of the following within 6 months prior to study entry: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, stroke or transient ischemic attack 11. Any of the following within 3 months prior to study entry: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, inflammatory bowel disease, pulmonary embolism or other uncontrolled thromboembolic event 12. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormally that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study 13. Planned vaccination with a live or live-attenuated vaccines 14. Participation in another clinical trial and any treatment with any investigational drug within 30 days prior to randomization 15. Any illness or problem including geographic, psychiatric or psychological which is incompatible with being monitored during the trial 16. Patients with reproductive potential who do not agree to use effective method of contraception during the treatment 17. Person deprived of their liberty or under protective custody or guardianship
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biological activity of chemotherapy | 18 weeks after randomisation | Biological activity of chemotherapy as defined as \< 5 CTCs per 7.5 ml at the end of chemotherapy with docetaxel or cabazitaxel. |
Countries
France
Outcome results
None listed