Randomized Multicenter, Phase III Trial Evaluating the Safety of 2 Schedules of Cabazitaxel (Bi-weekly Versus Tri-weekly) Plus Prednisone in Elderly Men (≥ 65years) With mCRPC Previously Treated With a Docetaxel-containing Regimen
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 196
- 试验地点
- 31
- 主要终点
- Number of grade ≥ 3 neutropenia and/or neutropenic complications
研究概览
简要总结
The purpose of this study is to evaluate the incidence of grade ≥ 3 neutropenia and/or neutropenic complications (febrile neutropenia, neutropenic infection) with two schedules of cabazitaxel (bi-weekly versus tri-weekly) plus prednisone in elderly men (≥ 65 years) with mCRPC previously treated with a docetaxel-containing regimen.
详细描述
Randomized, open-label, phase 3 trial in mCRPC patients aged ≥ 65 years.
Number of subjects:
Total:170 to 200 (85 to 100 per arm)
Treatment:
- Arm A : cabazitaxel 25 mg/m² on Day 1 of a 3-week cycle plus daily prednisone or
- Arm B: cabazitaxel 16 mg/m² on Day 1 and Day 15 of a 4-week cycle plus daily prednisone.
- Treatment will be continued for a maximum of 10 cycles unless there is documented disease progression or unacceptable toxicity.
- Standard cabazitaxel premedication will be used
- Prophylactic G-CSF (GRANOCYTE) will be injected from Day 3 to Day 7 after every administration cycle of cabazitaxel· All new hormonal treatment, including ODM-201, prior to study entry is allowed.
- Patients who received Radium-223 are eligible for this study
- Treatment with LHRH should not be discontinued.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Patient aged ≥ 65 years with mCRPC previously treated with docetaxel
- •Medical or surgical castration with castrate level of testosterone (< 50 ng/dl) based on the EAU definition of castrate level of testosterone
- •Progressive disease according to PCWG2
- •Histologically proven prostate carcinoma
- •Health status allowing use of chemotherapy: G8 > 14; or G8 score ≤ 14 with geriatric assessment concluding to reversible impairment allowing use of chemotherapy
- •ECOG-PS 0, 1 or 2(ECOG-PS 2 should be related to prostate cancer)
- •Adequate hematologic, liver and renal functions:
- •Neutrophil count ≥1.5 109/L
- •Haemoglobin ≥10 g/ dL
- •Platelet count ≥100.109/L
- •Total bilirubin ≤ 1 the upper limit of normal (ULN)
- •Transaminases ≤ 1.5 ULN
- •Serum creatinine ≤ 2.0 ULN
- •Ongoing LHRH therapy at study entry
- •Signed informed consent
排除标准
- •History of severe hypersensitivity reaction (≥grade 3) to docetaxel
- •History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing drugs
- •Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus)
- •Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments) (see Appendix E)
- •PS >2 not related to prostate cancer disease
- •G8 ≤ 14 with geriatric assessment contra-indicating standard cabazitaxel regimen
- •Concomitant vaccination with yellow fever vaccine
- •Patient who cannot be regularly followed or cannot answer to quality of life questionnaires because of psychological, social, familial or geographic reasons
- •Participation in another clinical trial with any investigational drug within 30 days prior to study enrolment.
研究组 & 干预措施
Arm A
Cabazitaxel 25 mg/m² intravenously over 1 hour on Day 1of a 3-week cycle, plus prednisone (or prednisolone) 10 mg orally given daily for a maximum of 10 cycles (ie 30 weeks of treatment).
Prophylactic Granulocyte colony-stimulating factor G-CSF (Granocyte) will be injected from Day 3 to Day 7 after every administration of cabazitaxel.
干预措施: cabazitaxel (Drug)
Arm A
Cabazitaxel 25 mg/m² intravenously over 1 hour on Day 1of a 3-week cycle, plus prednisone (or prednisolone) 10 mg orally given daily for a maximum of 10 cycles (ie 30 weeks of treatment).
Prophylactic Granulocyte colony-stimulating factor G-CSF (Granocyte) will be injected from Day 3 to Day 7 after every administration of cabazitaxel.
干预措施: Prednisone (Drug)
Arm A
Cabazitaxel 25 mg/m² intravenously over 1 hour on Day 1of a 3-week cycle, plus prednisone (or prednisolone) 10 mg orally given daily for a maximum of 10 cycles (ie 30 weeks of treatment).
Prophylactic Granulocyte colony-stimulating factor G-CSF (Granocyte) will be injected from Day 3 to Day 7 after every administration of cabazitaxel.
干预措施: Granulocyte colony-stimulating factor (G-CSF) (Drug)
Arm B
Cabazitaxel 16 mg/m2 on Day 1 and Day 15 of a 4-week cycle plus prednisone (or prednisolone) 10 mg per day up to 10 cycles (ie 40 weeks of treatment). Prophylactic Granulocyte colony-stimulating factor G-CSF (Granocyte) will be injected from Day 3 to Day 7 after every administration of cabazitaxel.
干预措施: cabazitaxel (Drug)
Arm B
Cabazitaxel 16 mg/m2 on Day 1 and Day 15 of a 4-week cycle plus prednisone (or prednisolone) 10 mg per day up to 10 cycles (ie 40 weeks of treatment). Prophylactic Granulocyte colony-stimulating factor G-CSF (Granocyte) will be injected from Day 3 to Day 7 after every administration of cabazitaxel.
干预措施: Prednisone (Drug)
Arm B
Cabazitaxel 16 mg/m2 on Day 1 and Day 15 of a 4-week cycle plus prednisone (or prednisolone) 10 mg per day up to 10 cycles (ie 40 weeks of treatment). Prophylactic Granulocyte colony-stimulating factor G-CSF (Granocyte) will be injected from Day 3 to Day 7 after every administration of cabazitaxel.
干预措施: Granulocyte colony-stimulating factor (G-CSF) (Drug)
结局指标
主要结局
Number of grade ≥ 3 neutropenia and/or neutropenic complications
时间窗: Up to 11 months
To evaluate the incidence of grade ≥ 3 neutropenia (measured at Day 7 and Day 14) and/or neutropenic complications (febrile neutropenia, neutropenic infection) with two schedules of cabazitaxel (bi-weekly versus tri-weekly) plus prednisone in elderly men (≥ 65 years) with mCRPC previously treated with a docetaxel-containing regimen. with two schedules of -+cabazitaxel (bi-weekly versus tri-weekly) plus prednisone in elderly men with mCRPC previously treated with a docetaxel-containing regimen
次要结局
- Radiological progression-free survival (rPFS)(Up to 11 months)
- Time to PSA progression(Up to 11 months)
- Adverse events(Up to 11 months)
- Time to first symptomatic Skeletal-Related Event (SRE) and incidence of SREs(Up to 11 months)
- Prostate-specific antigen (PSA) response rate(Up to 11 months)
- Objective response rate (ORR) in measurable lesions (RECIST criteria 1.1 - only on metastasis(Up to 11 months)
- Dose reductions(through study completion, an average of 40 weeks)
- Time to opioid treatment (if relevant)(Up to 11 months)
- Quality of Life (FACT-P)(Up to 11 months)
- Factors influencing survival(Up to 11 months)
- Dose delay(Up to 11 months)
- Time to onset of grade ≥3 neutropenia(Up to 11 months)
- Grade ≥3 neutropenia duration ( from date of onset of grade ≥ 3 until grade ≤ 2)(Up to 11 months)
- Overall Survival (OS)(up to 11 months)
- Time to onset of grade ≥3 neutropenia by cycle(Up to 11 months)