Phase I/II Open Label Dose Escalation Study of the 17α-Hydroxylase/ C17,20-Lyase Inhibitor, Abiraterone Acetate in Hormone Refractory Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 66
- 主要终点
- Phase 1: Maximum Tolerated Dose (MTD) of Abiraterone Acetate
研究概览
简要总结
The purpose of this study is to evaluate the safety, pharmacokinetics, pharmacodynamics, and anti-tumor activities of abiraterone acetate (also referred to as CB7630) in patients with hormone refractory prostate cancer (HRPC).
详细描述
This is an open-label (identity of assigned study drug will be known) study to evaluate the safety, pharmacokinetics (study of what the body does to a drug), pharmacodynamics (study of what a drug does to the body), and anti-tumor activities of abiraterone acetate (also known as CB7630) in patients with HRPC. The study will be conducted in 2 phases (Phase 1 and Phase 2). In the first part of the study (Phase 1), the maximum tolerated dose (MTD) of abiraterone acetate will be determined for use in the second part of the study (Phase 2) where the number of patients who achieve at least a 50% decrease in prostate specific antigen (PSA) during treatment with abiraterone acetate will be assessed (MTD from Phase 1). Abiraterone acetate will be taken orally (by mouth) in fed and fasted patients once daily. Doses of abiraterone acetate (starting at 250 mg up to a maximum of 2000 mg) will be taken for 28-day treatment periods to determine the MTD. Patients will take MTD of abiraterone acetate for up to twelve 28 day cycles (12 months; patients will be given the option of staying on abiraterone acetate treatment if they are deriving benefit). In Phase 2, prednisone or dexamethasone will be administered concurrently with abiraterone acetate. Serial pharmacokinetic and pharmacodynamic samples will be collected and safety will be monitored throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Histologically confirmed adenocarcinoma of the prostate
- •No prior therapy with chemotherapy for prostate cancer
- •Ongoing gonadal androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) analogues or orchiectomy
- •Testosterone <50 ng/dL
- •Progressive disease after androgen deprivation
- •The presence of objective metastatic disease is NOT required for study eligibility
- •Demonstrate disease progression after antiandrogen withdrawal
- •Eastern Cooperative Oncology Group (ECOG) performance status score = 0-1
- •Laboratory values within protocol-defined parameters
- •Systolic blood pressure <160 mmHg and diastolic blood pressure <110mmHg documented on at least 3 different days
- •Baseline adrenocorticotropic hormone (ACTH) stimulation test demonstrating a peak cortisol >18 µg/dL
- •Agrees to protocol-defined use of effective contraception
- •Life expectancy of >=12 weeks
- •Same as Phase 1 criteria with addition of following criteria
- •Neoadjuvant or adjuvant chemotherapy is only allowed if the last dose is >1 year from Cycle 1 Day 1
- •Target or non-target abnormalities must be present either on screening bone scan, computed tomography or magnetic resonance imaging
- •No prior treatment with ketoconazole for the management of androgen independent prostate cancer
排除标准
- •Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart) any herbal product known to decrease prostate specific antigen (PSA) levels (eg, saw palmetto and PC-SPES), or any systemic corticosteroid within 4 weeks prior to first dose of study drug
- •Initiation of bisphosphonate therapy within 4 weeks prior to first dose of study drug
- •Therapy with supplements or complementary medicines/botanicals within 4 weeks of first dose of study drug, except for any combination of the following: conventional multivitamin supplements, selenium, lycopene, soy supplements
- •Prior radiation therapy completed <4 weeks prior to enrollment
- •Prior chemotherapy for hormone refractory prostate cancer
- •Any currently active second malignancy, other than non-melanoma skin cancer
- •Systolic blood pressure >=160 mmHg or diastolic blood pressure >=110 mmHg measured on at least 2 occasions
- •NYHA Class III or IV congestive heart failure
- •Myocardial infarction within the 6 months prior to the first dose of study drug
- •Serious intercurrent infections or nonmalignant medical illnesses that are uncontrolled
- •Active psychiatric illnesses/social situations that would limit compliance with protocol requirements
- •Active or uncontrolled autoimmune disease that may require corticosteroid therapy during study
- •Same as phase 1 with the following addition
- •Abnormal electrocardiogram, including any finding which would interfere with assessment of intervals (patients with long QT syndrome, bundle branch blocks or hemiblocks are prohibited)
研究组 & 干预措施
Phase I Dose Escalation
干预措施: Abiraterone acetate (Drug)
Phase II Dose Treatment
干预措施: Abiraterone acetate (Drug)
Phase II Dose Treatment
干预措施: prednisone/prednisolone or dexamethasone (Drug)
结局指标
主要结局
Phase 1: Maximum Tolerated Dose (MTD) of Abiraterone Acetate
时间窗: Up to Cycle 12
The MTD is the highest dose of a drug or treatment that does not cause unacceptable side effects.
Phase 2: Participants With Greater Than or Equal to 50 Percent Decline in Prostate Specific Antigen (PSA)
时间窗: Up to 12 weeks from start of treatment
Number of participants with greater than or equal to 50 percent decrease in PSA levels were assessed. PSA decline was evaluated according to (Prostate Specific Antigen Working Group) PSAWG criteria. Decrease in PSA levels represented improvement.
次要结局
- Phase 1: Maximum Plasma Concentration (Cmax) of Abiraterone Acetate(At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3.)
- Phase 1: Time to Reach the Maximum Plasma Concentration (Tmax) of Abiraterone Acetate(At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3)
- Phase 1: Area Under the Plasma-Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Abiraterone Acetate(At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3)
- Phase 1: Area Under the Plasma-Concentration-time Curve From Time 0 to Infinite Time (AUCINF_obs) of Abiraterone Acetate(At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3)
- Phase 1: Terminal Half-life (HL_Lambda_z) of Abiraterone Acetate(At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3)
- Phase 1: Total Body Clearance (Cl_F_obs) of Abiraterone Acetate(At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3)
- Phase 1: Volume of Distribution (Vz_F_obs) of Abiraterone Acetate(At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3)
- Phase 2: Radiographic Progression Free Survival (RAD-PFS)(Up to 12 weeks from start of treatment)
- Phase 2: PSA Progression Free Survival (PSA-PFS)(Up to 12 weeks from start of treatment)
- Phase 2: Radiographic Objective Response Rate (RAD-ORR)(Up to 12 weeks from start of treatment)
- Phase 2: Time to PSA Progression(Up to 12 weeks from start of treatment)
- Phase 2: Duration of PSA Response(Up to 12 weeks from start of treatment)
- Phase 2: Participants With Change in Eastern Cooperative Oncology Group (ECOG) Performance Status Score(Up to 12 weeks from start of treatment)
- Phase 2: Overall Survival(Up to Month 60)
- Phase 2: Duration of Objective Response(Up to 12 weeks from start of treatment)