A Phase III of Cabazitaxel and Pelvic Radiotherapy in Localized Prostate Cancer and High-risk Features of Relapse

Prior treatment

• Patients who received any other investigational drugs within the 30 days prior to the start of cabazitaxel.
• Previous pelvic irradiation that make prostatic irradiation impossible
• Patients already included in another therapeutic trial involving an experimental drug
• Concomitant prohibited treatment. Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (see Appendix 6). A one week wash-out period is necessary for patients who are already on these treatments

Other illness

• Other prior malignancy within the last 5 years, except basal cell skin cancer
• Physical or psychological condition that would preclude study compliance
• Hypersensitivity to cabazitaxel (hypersensitivity reaction ≥grade 3), to other taxanes, or to any excipients of the formulation including polysorbate 80
• Patients with significantly altered mental status prohibiting the understanding of the study or with psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
• Severe GI disorders precluding pelvic irradiation

Lab values

• Patients with other known concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as:
  • infection,
  • cardiac disease such as uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within one year, left ventricular ejection fraction (LVEF) \> grade 2,
  • uncontrolled diabetes mellitus,
  • current active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, stable chronic liver disease per investigator assessment),
  • renal disease,
  • active GI tract ulceration, malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with active, uncontrolled ulcerative colitis are also excluded,
  • known severely impaired lung function (spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO) 70% or less of normal and O2 saturation of 88% or less at rest on room air).

Other

• Individual deprived of liberty or placed under the authority of a tutor.

• Any T histologically confirmed adenocarcinoma of the prostate
• No clinically or radiologically suspected metastases, including no enlarged pelvic lymph nodes (\> 1 cm in small diameter)
• Gleason score ≥ 6
• Meets at least 2 of the following criteria for high-risk:
  • Gleason score ≥ 8
  • T3 or T4 disease (T3 defined by MRI is acceptable)
  • Prostate-specific antigen equal or greater than 20 ng/mL
• No prior treatment for prostate cancer except lymph node dissection (patients with pN- and pN+ disease can be accrued) or ADT (started up to 6 weeks before randomization).
• 18 years ≤ Age ≤ 75 years
• Eastern Cooperative Oncology Group (ECOG) 0-1 performance status
• Expected life expectancy of more than 10 years
• Absolute neutrophil count ≥ 1.5 x 10⁹/L
• Platelets ≥ 100 x 10⁹/L
• Hb ≥ 9.0 g/dL
• Hepatic function: serum bilirubin ≤ 1 upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
• Renal function (creatinine clearance using the Chronic Kidney Disease Epidemiology group (CKD-EPI) formula ≥ 60 mL/min).
• Potentially reproductive patients must agree to use an effective contraceptive method while on treatment and for 6 months after the final dose of investigational product.
• Patients must be affiliated to a Social Security System or should fulfill the country legislation for clinical trials.
• Patients who have received the information sheet and signed the informed consent form.
• Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures