A Randomized Phase III, Factorial Design, of Cabazitaxel and Pelvic Radiotherapy in Patients With Localized Prostate Cancer and High-risk Features of Relapse
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- UNICANCER
- 入组人数
- 761
- 试验地点
- 1
- 主要终点
- progression free survival
研究概览
简要总结
The objective of this study is to assess the effect of neoadjuvant cabazitaxel and pelvic radiotherapy in combination with androgen deprivation therapy (ADT)-radiotherapy on clinical progression-free survival 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.
详细描述
Eligible patients can be randomized via the TENALEA web site process that insure centralization of the randomization.
Randomization will be performed according a 1:1:1:1 ratio. The randomization will be stratified (by minimization) according to the number of risk factors (2 vs.3), disease extent (pN- vs. pN+ vs. pNx) and the site.
The minimization will be defined with a similar weight for all 3 stratification factors and a probability of assigning the treatment that minimize the imbalance equal to 80%.
The main analysis of progression-free survival (PFS) will be event driven (> 247 events). It will likely be performed when the median follow-up is approximately 6 years, i.e. 4 years after the inclusion of the last patient (assuming an accrual of 4 years).
A long-term analysis (allowing for robust PFS and overall survival (OS) data) will also be performed when the follow-up is approximately 10 years. Its exact timing will be discussed with the steering committee and the IDMC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Patients with other known concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as:
- •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 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.
- •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
- •Severe GI disorders precluding pelvic irradiation
- •Patients already included in another therapeutic trial involving an experimental drug
- •Individual deprived of liberty or placed under the authority of a tutor.
- •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
研究组 & 干预措施
ADT + pelvic RT
ADT for a total duration of 3 years i.e. luteinizing hormone-releasing hormone (LHRH) agonist or LHRH antagonist +/-Peripheral anti-androgen
Pelvic RT (by IMRT or IGRT protocol):
- Phase 1: pelvic radiotherapy (prostate, seminal vesicles, ilio-obturator, presacral lymph nodes) (46 or 50 Gy according to the center)
- Phase 2: prostate-only boost (EBRT) up to 74-78 Gy
干预措施: Pelvic radiotherapy (Radiation)
ADT + Cabazitaxel + prostate RT
ADT Cabazitaxel: 4 CT cycles
Prostate-only RT (IMRT or IGRT):
- Phase 1: prostate + seminal vesicle radiotherapy (46 or 50 Gy according to the center)
- Phase 2: prostate-only boost (EBRT) up to 74-78 Gy
干预措施: Cabazitaxel (Drug)
ADT + Cabazitaxel + prostate RT
ADT Cabazitaxel: 4 CT cycles
Prostate-only RT (IMRT or IGRT):
- Phase 1: prostate + seminal vesicle radiotherapy (46 or 50 Gy according to the center)
- Phase 2: prostate-only boost (EBRT) up to 74-78 Gy
干预措施: prostate radiotherapy (Radiation)
ADT + cabazitaxel + pelvic RT
ADT Cabazitaxel: 4 CT cycles
Pelvic RT (IMRT or IGRT):
- Phase 1: pelvic radiotherapy (prostate, seminal vesicles, ilio-obturator, presacral lymph nodes) (46 or 50 Gy according to the center)
- Phase 2: prostate-only boost (EBRT) up to 74-78 Gy
干预措施: Cabazitaxel (Drug)
ADT + cabazitaxel + pelvic RT
ADT Cabazitaxel: 4 CT cycles
Pelvic RT (IMRT or IGRT):
- Phase 1: pelvic radiotherapy (prostate, seminal vesicles, ilio-obturator, presacral lymph nodes) (46 or 50 Gy according to the center)
- Phase 2: prostate-only boost (EBRT) up to 74-78 Gy
干预措施: Pelvic radiotherapy (Radiation)
ADT + prostate radiotherapy
ADT for a total duration of 3 years: LHRH agonist or LHRH antagonist +/- anti-androgen
Prostate-only RT (IMRt or IGRT):
- Phase 1: prostate + seminal vesicle radiotherapy (46 or 50 Gy according to the center)
- Phase 2: prostate-only boost (EBRT) up to 74-78 Gy
干预措施: prostate radiotherapy (Radiation)
结局指标
主要结局
progression free survival
时间窗: 10 years
次要结局
- acute toxicity(10 years)
- overall survival(10 years)
- metastases-free survival(10 years)
- impact of treatment on serum testosterone(10 years)
- predictive biomarkers of treatment efficacy(10 years)
- quality of life(10 years)
- prostate-specific antigen response at 3 months(10 years)
- biochemical progression-free survival(10 years)
- local relapse-free survival(10 years)
- prostate cancer-specific survival(10 years)
- long-term toxicity(10 years)