localized prostate cancer with high-risk features of relapse MedDRA version: 14.1 Level: PT Classification code 10060862 Term: Prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
UNICANCER
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1) Any T histologically confirmed adenocarcinoma of the prostate 2) No clinically or radiologically suspected metastases, including no enlarged pelvic lymph nodes (> 1 cm in small diameter) 3) Gleason score =7 4) 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 5) No prior treatment for prostate cancer except lymph node dissection (patients with pN- and pN+ disease can be accrued). 6) 18 years = Age= 75 years 7) ECOG 0-1 performance status 8) Expected life expectancy of more than 10 years 9) Absolute neutrophil count = 1.5 x 10^9/L 10) Platelets = 100 x 10^9/L 11) Hb = 9.0 g/dL 12) Hepatic function: serum bilirubin = 1 ULN; AST and ALT = 2.5 x ULN 13) Renal function (creatinine clearance using the CKD-EPI formula (Chronic Kidney Disease Epidemiology group) = 60 mL/min). 14) 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. 15) Patients must be affiliated to a Social Security System or should fulfill the country legislation for clinical trials. 16) Patients who have received the information sheet and signed the informed consent form. 17) Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 524 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 524
Exclusion criteria
Exclusion criteria: 1) Patients with other known concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as: a- infection, b- cardiac disease such as uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within one year, LVEF > grade 2, c- uncontrolled diabetes mellitus, d- current active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, stable chronic liver disease per investigator assessment), e- renal disease, f- 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, g- known severely impaired lung function (spirometry and DLCO 70% or less of normal and O2 saturation of 88% or less at rest on room air). 2) Other prior malignancy within the last 5 years, except basal cell skin cancer 3) Physical or psychological condition that would preclude study compliance 4) Hypersensitivity to cabazitaxel (hypersensitivity reaction =grade 3), to other taxanes, or to any excipients of the formulation including polysorbate 80 5) 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. 6) Patients who received any other investigational drugs within the 30 days prior to the start of cabazitaxel. 7) Previous pelvic irradiation that make prostatic irradiation impossible 8) Severe GI disorders precluding pelvic irradiation 9) Patients already included in another therapeutic trial involving an experimental drug 10) Individual deprived of liberty or placed under the authority of a tutor. 11) 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the efficacy of both neoadjuvant cabazitaxel and pelvic radiotherapy in combination with ADT-radiotherapy in patients with high-risk localized prostate cancer, with a stringent selection of patients with at least 2 high-risk features, in a 2 by 2 factorial trial, in terms of clinical progression-free survival (cPFS).;Secondary Objective: ? Prostate-specific antigen response at 3 months ? Biochemical progression-free survival ? Metastases-free survival ? Local relapse-free survival ? Overall survival ? Prostate cancer-specific survival ? Acute toxicity ? Impact of treatment on serum testosterone ? Long-term toxicity (including toxicity related to radiotherapy) ? Predictive biomarkers of treatment efficacy ? Quality of life;Primary end point(s): Clinical Progression-Free Survival (cPFS) at 6 years, the event being defined by a metastatic relapse, a local progression or the patient death (all causes). A metastatic relapse will be defined by the appearance of undebatable metastases on imaging (mainly bone scan and CT-Scan). A local relapse will be defined as an indisputable local progression of prostate cancer by clinical examination or imaging. Pathological confirmation of the local progression is highly recommended. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? The prostate-specific antigen response at 3 months will be defined as a serum PSA value (= 0.2 ng/mL) ? The biochemical progression-free survival is defined as the time from randomization to the date of PSA relapse (evaluated according to Phoenix criteria i.e. nadir + 2 ng/mL) or death. ? The metastases-free survival is defined as the time from randomization to the date of the appearance of the metastases on imaging (mainly bone scan and CT-scan) or death. ? The local relapse-free survival is defined as the time from randomization to the date of the appearance of the first local relapse or death. ? The overall survival will be calculated from the date of randomization to the date of death from any cause or date of the last follow-up. ? The prostate cancer-specific survival will be calculated from the date of randomization to the date of the death due to prostate cancer ? The acute toxicity (i.e. during the treatment period), will be evaluated according to the NCI-CTC v4.0 criteria ? The impact of treatment on serum testosterone will be evaluated at baseline, 6 months then yearly. ? The long-term toxicity (potency, cardiac, hot flashes and late toxicity related to radiotherapy or chemotherapy) will be evaluated at 1 year, 2 years and 5 years. The toxicity related to the radiotherapy will be assessed using NCI-CTC v4.0 criteria. ? The predictive biomarkers of treatment efficacy will be assessed on archival biopsy specimens ? The quality of life will be evaluated with the QLQ –C30 and PR25 questionnaires at baseline, 6 months then yearly up to 5 years. | — |
Countries
France, Germany, Italy, Spain, United Kingdom
Contacts
Public ContactMuriel HABIBIAN
UNICANCER
Outcome results
None listed