A Phase 1b/2 Study to Assess the Safety and Efficacy of AMG 102 in Combination With Mitoxantrone and Prednisone in Subjects With Previously Treated Castrate Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 162
- 主要终点
- Phase 1b - Incidence of adverse events defined by dose-limiting toxicities
研究概览
简要总结
The primary objectives of this study are the following:
Phase 1b: To identify a safe dose level of AMG 102, up to 15 mg/kg Q3W, to combine with mitoxantrone and prednisone (MP) Phase 2: To estimate with adequate precision the effect of the addition of AMG 102 to MP, compared with placebo plus MP, as assessed by the hazard ratio (HR) for overall survival (OS) of previously treated subjects with castrate-resistant prostate cancer (CRPC)
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
- Double (Participant, Investigator)
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
- •Pathologically confirmed adenocarcinoma of the prostate
- •Radiographic evidence of metastatic disease
- •Progressive disease meeting at least one of the following criteria:
- •a sequence of at least 2 rising PSA values measured at a minimum of 1 week apart with a 2 ng/mL minimum starting value, or
- •progression according to RECIST criteria for measurable lesions, or
- •appearance of 2 or more new lesions on bone scan.
- •History of prior taxane-based chemotherapy for metastatic prostate cancer
- •For patients without a history of surgical castration, continued GnRH analog administration is required
- •ECOG Performance status of 0 or 1
- •Life expectancy ≥ 3 months
排除标准
- •Treatment with external beam radiotherapy ≤ 14 days before enrollment or radiopharmaceutical ≤8 weeks
- •≤ 4 weeks since receipt of most recent prior chemotherapy, non-GnRH analog hormonal therapy (except for continuing corticosteroids) or other systemic therapy to treat prostate cancer and <6 weeks since receipt of prior bevacizumab.
- •Known CNS metastases (epidural disease is allowed if it has been treated and there is no progression in the treated area).
- •Significant cardiovascular disease
- •LVEF < 50% by MUGA or ECHO
- •Treatment of infection with systemic anti-infectives within 7 days before enrollment (with the exception of uncomplicated urinary tract infection)
- •Concurrent or prior (within 7 days of enrollment) anticoagulation therapy, except that use of low dose coumarin-type anticoagulants or heparins for prophylaxis against central venous catheter thrombosis is allowed
- •Major surgical procedure ≤30 days before enrollment or not yet recovered from prior major surgery
- •Presence of peripheral edema > Grade 2
- •Known positive test for HIV, hepatitis C, chronic or active hepatitis B
- •Serious or non-healing wound
- •Unable to begin protocol specified treatment within 7 days after enrollment
- •Other investigational procedures are excluded.
研究组 & 干预措施
Phase 1b - AMG 102
Phase 1b is an open-label study with AMG 102 at 15mg/kg de-escalating to 7.5mg/kg and 5mg/kg if needed, will be administered by IV Q3W in combination with MP.
干预措施: AMG 102 (Drug)
Phase 1b - AMG 102
Phase 1b is an open-label study with AMG 102 at 15mg/kg de-escalating to 7.5mg/kg and 5mg/kg if needed, will be administered by IV Q3W in combination with MP.
干预措施: Mitoxantrone (Drug)
Phase 1b - AMG 102
Phase 1b is an open-label study with AMG 102 at 15mg/kg de-escalating to 7.5mg/kg and 5mg/kg if needed, will be administered by IV Q3W in combination with MP.
干预措施: Prednisone (Drug)
Phase 2 Arm A - AMG 102 + MP
AMG 102 safe dose level in phase 1b in combination with MP, will be administered by IV Q3W.
干预措施: AMG 102 (Drug)
Phase 2 Arm A - AMG 102 + MP
AMG 102 safe dose level in phase 1b in combination with MP, will be administered by IV Q3W.
干预措施: Mitoxantrone (Drug)
Phase 2 Arm A - AMG 102 + MP
AMG 102 safe dose level in phase 1b in combination with MP, will be administered by IV Q3W.
干预措施: Prednisone (Drug)
Phase 2 Arm C- PLACEBO
Placebo in combination with MP, will be administered by IV Q3W.
干预措施: Mitoxantrone (Drug)
Phase 2 Arm C- PLACEBO
Placebo in combination with MP, will be administered by IV Q3W.
干预措施: Placebo (Drug)
Phase 2 Arm C- PLACEBO
Placebo in combination with MP, will be administered by IV Q3W.
干预措施: Prednisone (Drug)
Phase 2 Arm B - AMG 102 + MP
Safe dose level in phase 1b of AMG 102 + MP will be administered by Q3W
干预措施: AMG 102 (Drug)
Phase 2 Arm B - AMG 102 + MP
Safe dose level in phase 1b of AMG 102 + MP will be administered by Q3W
干预措施: Mitoxantrone (Drug)
Phase 2 Arm B - AMG 102 + MP
Safe dose level in phase 1b of AMG 102 + MP will be administered by Q3W
干预措施: Prednisone (Drug)
结局指标
主要结局
Phase 1b - Incidence of adverse events defined by dose-limiting toxicities
时间窗: 21 days after the 6th subjects has recieved 1st cycle of AMG 102 in combination with MP
Phase 2 - Overall survival
时间窗: Entire Study
次要结局
- Phase 1b - Incidence of adverse events, abnormal laboratory values not defined as dose limiting toxicities(Treatment Period)
- Phase 1b - Incidence of anti-AMG 102 antibody formation(Entire Study)
- Phase 1b - Cmax and Cmin of AMG 102 concentration(Treatment Period)
- Phase 2 - Progression-free survival(Entire Study)
- Phase 2 - Maximum percentage reduction in PSA level(Entire Study)
- Phase 2 - PSA response rate (≥50% reduction in PSA values from baseline)(Entire Study)
- Phase 2 - Objective response rate (CR and PR per RECIST with modifications)(Entire Study)
- Phase 2 - Patient Report Outcome including pain-specific measures(Treatment Period)
- Phase 2 - Incidence of adverse events and significant laboratory value changes from baseline(Treatment Period)
- Phase 2 - Incidence of anti-AMG 102 antibody formation(Entire Study)
- Phase 2 - Cmax and Cmin of AMG 102; Cmax and AUC for Mitoxantrone(Treatment Period)
- Phase 2 - Percentage change in PSA levels from baseline to 12 weeks (or earlier for those who discontinue therapy)(Treatment Period)