Phase Ib Dose Finding Study of Abiraterone Acetate Plus BEZ235 or BKM120 in Patients With Castration-resistant Prostate Cancer.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 3
- 主要终点
- Incidence of dose limiting toxicities (DLTs)
研究概览
简要总结
This is an open label study of abiraterone acetate in combination with BEZ235 and abiraterone acetate in combination with BKM120 in CRPC patients with abiraterone acetate failure.
详细描述
A dose-escalation part will first determine the maximum tolerated dose (MTD) and/or recomended dose for expansion (RDE) of abiraterone acetate in combination with BEZ235 and abiraterone acetate in combination with BKM120 in CRPC patients with abiraterone acetate failure.
Subsequently, the MTD and/or RDE of each combination will be investigated in two expansion treatment groups of CRPC patients who have failed abiraterone acetate therapy.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Adult males ≥ 18 years old
- •Eastern Cooperative Oncology Group Performance Status ≤ 2
- •Patient must have a castrate level of testosterone (<= 50 ng/dL or 1.7 nmol/L). ( Castrate status must be maintained by continued GnRH analogues unless patient has undergone surgical orchiectomy).
- •Histologically or cytologically confirmed diagnosis of advanced or metastatic prostate cancer.
- •Advanced or metastatic castration-resistant prostate cancer progression after abiraterone acetate failure
- •Patients should have no more than 2 lines of prior chemotherapies including cytotoxic agents
- •Discontinuation of all anti-androgen, anti-neoplastic or investigational treatment >= 4 weeks (6 weeks for bicalutamide).
排除标准
- •Previous treatment with PI3K pathway inhibitors (e.g. PI3K, AKT, mTOR inhibitor), ketoconazole, CYP17 inhibitors (exception of AA), or enzalutamide.
- •Patient has active uncontrolled or symptomatic CNS metastases
- •Inadequately controlled hypertension (e.g. systolic blood pressure >=160 mmHg or diastolic blood pressure >=95 mmHg)
- •Patient has a QTcF > 480 msec on the screening ECG (using the QTcF formula), has a short/long QT syndrome, or history of QT prolongation/Torsades de Pointes
- •Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs
- •Patient has a medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others)
- •Patients who experienced dose reductions and/or treatment interruptions due to abiraterone acetate related toxicities (i.e. serious AEs, AEs, liver toxicities during abiraterone acetate treatment
研究组 & 干预措施
Dose escalation: BEZ235 + Zytiga®
BEZ235 oral twice daily: 200 mg, 300 mg, and 400 mg dose levels to be tested in the dose escalation part in combination with abiraterone acetate Zytiga® abiraterone acetate oral once daily: 1000 mg taken with low dose prednisone as per the label
干预措施: BEZ235 (Drug)
Dose escalation: BKM120 + Zytiga®
BKM120 oral once daily: 60 mg, 80 mg and 100 mg dose levels to be tested in the dose escalation part in combination with abiraterone acetate Zytiga® abiraterone acetate oral once daily: 1000 mg taken with low dose prednisone as per the label
干预措施: BKM120 (Drug)
Dose expansion: BEZ235 + Zytiga®
BEZ235 oral twice daily: 200 mg, 300 mg, and 400 mg dose levels to be tested in the dose escalation part in combination with abiraterone acetate
Zytiga® abiraterone acetate oral once daily: 1000 mg taken with low dose prednisone as per the label
干预措施: BEZ235 (Drug)
Dose Expansion: BKM120 + Zytiga®
BKM120 oral once daily: 60 mg, 80 mg and 100 mg dose levels to be tested in the dose escalation part in combination with abiraterone acetate Zytiga® abiraterone acetate oral once daily: 1000 mg taken with low dose prednisone as per the label
干预措施: BKM120 (Drug)
结局指标
主要结局
Incidence of dose limiting toxicities (DLTs)
时间窗: from days 1-35 in BEZ235/abiraterone acetate arm and from days 1-28 in BKM120/abiraterone acetate arm
Dose escalation part: Determine MTD and /or RDE of the combinations abiraterone acetate + BEZ235 and abiraterone acetate + BKM120 by assessing the incidence of DLTs in cycle 1
Prostate specific antigen (PSA) decline ≥ 30%
时间窗: At week 12 or later after treatment discontinuation
Dose expansion part: Assess anti-tumor activity of the combinations (abiraterone acetate + BEZ235 and abiraterone acetate + BKM120) in castration-resistant prostate cancer patients with abiraterone acetate failure as on treatment PSA progression according to prostate cancer working group criteria 2 (PCWG2) by assessing PSA decline ≥ 30% at Week 12 or later.
次要结局
- radiological Progression Free Survival as per RECIST 1.1 and PCWG2(Every 12 weeks until disease progression)
- radiological Response Rate according to RECIST 1.1(Every 12 weeks until disease progression)
- Overall Survival(From treatment start until 75% of deaths from any cause have occurred)
- Changes in ECG (electrocardiogram)(Treatment start until 30 days after the last dose)
- Changes in mood scales(Treatment start until 30 days after the last dose)
- Number and percentage of patients with laboratory abnormalities(Treatment start until 30 days after the last dose)
- Changes in vital signs(Treatment start until 30 days after the last dose)
- Number of patients with at least one adverse event(Treatment start until 30 days after the last dose)