An Open Label, Phase II, Multicenter Study to Evaluate the Efficacy and Safety of a Recombinant Humanized Antibody to HER2 (Pertuzumab) Administered Every 3 Weeks to Patients With Hormone-Refractory Prostate Cancer Who Have Not Been Treated With Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 68
- 主要终点
- Percentage of Participants With Confirmed, Objective Response, Non-Response or Progressive Disease by PSA Levels Within the First 24 Weeks of Treatment With Pertuzumab
研究概览
简要总结
This study will evaluate the efficacy and safety of intravenous (IV) pertuzumab in participants with hormone-refractory prostate cancer who have had no previous chemotherapy. Participants will be enrolled in two stages, the first (Cohort A) at a lower 420-mg dose and the second (Cohort B) at a higher 1050-mg dose based upon observations in Cohort A. Up to 50 participants may enter either cohort, for a total enrollment between 46 and 73 participants across 9 study centers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Adults greater than (>) 18 years of age
- •Histologically documented adenocarcinoma of the prostate resistant to hormone therapy, progressed at 4 to 6 weeks following anti-androgen withdrawal
- •Prostate-specific antigen (PSA) values at least 20 ng/mL among those with asymptomatic or mildly symptomatic disease
- •Karnofsky performance status (KPS) at least 80 percent (%)
- •Castrate testosterone less than (<) 50 ng/dL
- •Life expectancy at least 12 weeks
- •Left ventricular ejection fraction (LVEF) at least 50%
- •Adequate hematologic, hepatic, and renal function
排除标准
- •Prior chemotherapy, radionucleotide therapy, or immunotherapy for prostate cancer
- •Systemic corticosteroids within 1 month prior to Screening
- •Bisphosphonates within 6 months, narcotic analgesics within 2 weeks, or any investigational agent with 28 days of study drug
- •Prior cumulative doxorubicin dose of > 360 mg/m^2 or equivalent
- •Central nervous system (CNS) or pulmonary metastases
- •Other malignancies, except adequately treated basal or squamous cell skin cancer
- •Significant cardiovascular disease
- •Active/uncontrolled concurrent illness or infection
- •Major surgery or traumatic injury within 4 weeks of study drug
研究组 & 干预措施
Pertuzumab 1050 mg (Cohort B)
Participants in Cohort B will receive 1050 mg pertuzumab via IV infusion on Day 1 of each 3-week cycle. At the end of 3 treatment cycles, response will be evaluated to determine whether additional participants will be enrolled for treatment. If a second stage of enrollment occurs, participants may continue treatment until disease progression or unacceptable toxicity.
干预措施: Pertuzumab (Drug)
Pertuzumab 420 mg (Cohort A)
Participants in Cohort A will receive an IV loading dose of 840 milligrams (mg) pertuzumab followed by 420 mg via IV infusion on Day 1 of each 3-week cycle. At the end of 3 treatment cycles, response will be evaluated to determine whether additional participants will be enrolled for treatment. If a second stage of enrollment occurs, participants may continue treatment until disease progression or unacceptable toxicity.
干预措施: Pertuzumab (Drug)
结局指标
主要结局
Percentage of Participants With Confirmed, Objective Response, Non-Response or Progressive Disease by PSA Levels Within the First 24 Weeks of Treatment With Pertuzumab
时间窗: Screening, Every 3 weeks up to Week 24
Objective PSA response rate was determined according to Prostate Specific Antigen Working Group (PSAWG) guidelines. All participants achieving a drop in PSA of greater than or equal to (≥) 50 percent (%) from baseline (confirmed with a second value at least 4 weeks later) fulfilled the criteria of a PSA response. The confirmatory second value had to be at least 50% lower than baseline, but could be higher than the first drop in PSA. Confirmatory value could not be 50% higher compared to first drop in PSA. The date of response was the date the first 50% (or greater) decline was observed. Progressive disease (PD) was defined by a minimum of three consecutive serum PSA measurements obtained at least 7 days apart within the previous 3 months of start of trial, which documented progressively increasing values. Non-response was defined as neither PD nor Response.
次要结局
- Time to Disease Progression(Screening, Every 3 weeks up to a maximum of 18 months)
- Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria(Screening, Weeks 6, 12, 24, 36 and 48)
- Time to Response(Screening, Every 3 weeks for a maximum of 18 months)
- Duration of Response According to PSA Levels(Baseline, Every 3 weeks for a maximum of 18 months)
- Duration of Response According to RECIST Criteria(Baseline, Weeks 6, 12, 24, 36 and 48)
- Percentage of Participants Without Progression(Screening, Weeks 3, 6, 9 and 12)
- Time to Prostate Cancer Pain Progression(Every 3 weeks up to a maximum of 18 weeks)
- Overall Survival(Screening, Every 3 weeks up to a maximum of 18 months)
- Time to Treatment Failure(Every 3 weeks up to a maximum of 18 weeks)
- Change From Baseline in Bone Alkaline Phosphatase(Screening, Weeks 6, 12, 24, 36 and 48)
- Change From Baseline in N-Telopeptide(Screening, Weeks 6, 12, 24, 36 and 48)
- Area Under the Concentration Curve Extrapolated to Infinity (AUC0-Inf) of Pertuzumab(Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1, Day 8, and Day 15. Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1)
- AUC to Last Measurable Concentration (AUC0-last) of Pertuzumab(Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1, Day 8, and Day 15. Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1)
- Maximum Plasma Concentration of Pertuzumab(Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1, Day 8, and Day 15. Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1)
- Time to Maximum Plasma Concentration (Tmax) of Pertuzumab(Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1 and on Days 8 and 15, Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1)
- Terminal Elimination Half-Life (t1/2) of Pertuzumab(Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1, Day 8, and Day 15. Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1)
- Serum Clearance of Pertuzumab(Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1, Day 8, and Day 15. Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1)
- Volume of Distribution at Steady State of Pertuzumab(Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1, Day 8, and Day 15. Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1)
- Mean Residence Time (MRT) of Pertuzumab(Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1, Day 8, and Day 15. Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1)