A Randomized, Open Label, Multicenter, Phase III, 2-Arm Study of Androgen Deprivation With Leuprolide, +/- Docetaxel for Clinically Asymptomatic Prostate Cancer Subjects With a Rising PSA Following Definitive Local Therapy
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Sanofi
- 入组人数
- 413
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS) Rate at Month 36 in ITT Population
研究概览
简要总结
The primary objective was to evaluate and compare the efficacy of androgen deprivation with or without docetaxel as determined by the median progression free survival (PFS) over the period of 18-month therapy and at least 18-month follow-up.
The secondary objectives were:
- To assess cancer specific survival;
- To compare overall survival between the 2 treatment groups;
- To evaluate patient-reported outcomes including quality of life, fatigue, and sexual functioning as measured by 3 different assessments.
详细描述
The duration of the study per participant was to be at least 36 months, of which the treatment period was 18 months for all participants, followed by at least 18 months follow-up period.
Participants received study treatment for up to 18 months from the time of study therapy initiation or less if one of the following occurred: disease progression, unacceptable toxicity, death, participant refusal or treatment delay beyond the time frame that is permitted for each treatment.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of prostate adenocarcinoma pathologically confirmed
- •History of radical prostatectomy (pre-operative radiation therapy to the prostate or pelvis or salvage radiation after radical prostatectomy was allowed)
- •Demonstration of biochemical progression of disease based on prostate specific antigen (PSA) doubling time. The minimum PSA value for eligibility was greater than or equal to (>=)
- •PSA doubling time over three values must be equal to (=) 9 months with a minimum of 3 weeks between assessments
- •Serum testosterone >=100 nanogram per deciliter (ng/dL)
- •Karnofsky performance status (KPS) >=70 percent (%)
- •Adequate organ function as defined by the following laboratory criteria:
- •White blood cells >=3500 per cubic millimeter (mm^3)
- •Absolute neutrophil count (ANC) >=1500 per mm^3
- •Platelet count >=100,000 per mm^3
- •Hemoglobin >= 10.0 gram per deciliter (g/dL)
- •Total Bilirubin less than or equal to (<=) upper limit of normal (ULN) unless due to Gilbert's disease
- •Creatinine l <= 1.5 milligram per deciliter (mg/dL) or creatinine clearance >=60 cubic centimeters per minute
- •Aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase within pre-defined ranges
- •Previous hormonal therapy was allowed provided that the total duration of therapy did not exceed 6 months
- •Man of childbearing potential who was willing to consent to use effective contraception while on treatment and for at least 3 months thereafter
- •Participant who was willing and was able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
排除标准
- •Clinically significant cardiac disease (New York Heart Association Class III/IV), or severe debilitating pulmonary disease
- •Uncontrolled serious active infection
- •Anticipated duration of life < 2 years
- •Less than 5-year history of successful treatment for other cancers or concurrent active nonprostate cancer other than nonmelanoma dermatologic tumor
- •Peripheral neuropathy >=Grade 2
- •History of hypersensitivity reaction to Docetaxel or other drugs formulated with polysorbate 80, leuprolide, or bicalutamide
- •Prior chemotherapy within the past 10 years (except non-taxane based chemotherapy for treatment of other cancers); concurrent treatment on another clinical trial or with any other cancer therapy including chemotherapy, immunotherapy, radiotherapy (except salvage radiation therapy), chemoembolization therapy, cryotherapy
- •Other severe acute or chronic medical conditions including psychiatric disease, or significant laboratory abnormality requiring further investigation that may cause undue risk for the participant's safety, delay or prohibit protocol participation, or interfere with the interpretation of study results, and in the judgment of the investigator would make the participant inappropriate for entry into this study
- •Radiographic findings suspicious for metastatic disease in the treating physician's clinical judgment. Participant who had radiographically suspicious pelvic lymph nodes prior to radial prostatectomy, but who, at the time of enrollment did not have suspicious adenopathy was eligible. Participant was eligible even if he/she had tumor-containing pelvic adenopathy at the time of surgery as long as at the time of enrollment there was no radiographically evident nodal disease in the clinician's opinion
- •Participant was the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol
- •Participant unlikely to comply with protocol or research tests, for example, uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
- •Participant who participated in another clinical study/received investigational product within 30 days of screening
- •The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
研究组 & 干预措施
Docetaxel+Leuprolide+Bicalutamide
Participants received docetaxel 75 milligram per square meter (mg/m^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles (3 week cycle) along with leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
干预措施: Bicalutamide (Drug)
Docetaxel+Leuprolide+Bicalutamide
Participants received docetaxel 75 milligram per square meter (mg/m^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles (3 week cycle) along with leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
干预措施: Docetaxel (Drug)
Docetaxel+Leuprolide+Bicalutamide
Participants received docetaxel 75 milligram per square meter (mg/m^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles (3 week cycle) along with leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
干预措施: Leuprolide (Drug)
Leuprolide+Bicalutamide
Participants received leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
干预措施: Leuprolide (Drug)
Leuprolide+Bicalutamide
Participants received leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
干预措施: Bicalutamide (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) Rate at Month 36 in ITT Population
时间窗: Month 36
PFS rate at Month 36 was defined as probability of being progression-free at Month 36. PFS rate was estimated using the Kaplan-Meier method.
Progression-Free Survival (PFS) Rate at Month 36 in Testosterone Specific Evaluable Population
时间窗: Month 36
PFS rate at Month 36 was defined as probability of being progression-free at Month 36. PFS rate was estimated using the Kaplan-Meier method.
Median Progression-Free Survival (PFS) in Testosterone Specific Evaluable Population
时间窗: Randomization until PSA progression or radiographic progression or death due to prostate cancer, assessed up to Month 60
PFS was the time from randomization to the date of first documented PSA progression, or radiographic progression, or death due to prostate cancer in the absence of previous documentation of disease progression, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method.
Median Progression-Free Survival (PFS) in Intent-to-treat (ITT) Population
时间窗: Randomization until PSA progression or radiographic progression or death due to prostate cancer, assessed up to Month 60
PFS was the time from randomization to the date of first documented prostate specific antigen (PSA) progression, or radiographic progression, or death due to prostate cancer in the absence of previous documentation of disease progression, whichever occurred first. PSA progression was determined as: a) During treatment period: a 50 percent (%) increase from baseline, which was confirmed by a second value; b) During follow-up: detectable PSA (defined as PSA greater than or equal to 0.05 nanogram per millimeter \[ng/mL\]), which was confirmed by consecutive observation (not less than 2 weeks apart). Median PFS was estimated using the Kaplan-Meier method.
次要结局
- Overall Survival (OS): Number of Participants Who Died (All Cause)(Randomization until death due to any cause, assessed up to Month 60)
- Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Trial Outcome Index (TOI) Score at EOT(Baseline, EOT (up to Month 18))
- Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score at End of Treatment (EOT)(Baseline, EOT (up to Month 18))
- Change From Baseline in Multidimensional Assessment of Fatigue (MAF) Index Score at EOT(Baseline, EOT (up to Month 18))
- Change From Baseline in Erectile Function Domain of International Index of Erectile Function (EF-IIEF) Total Score at EOT(Baseline, EOT (up to Month 18))
- Cancer-Specific Survival: Number of Participants Who Died (Cancer-Specific)(Randomization until death due to prostate cancer, assessed up to Month 60)