An Open-label, Multi-center Phase I Dose-finding Study of RAD001 (Everolimus, Afinitor®) in Combination With BEZ235 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 4
- 主要终点
- Probability of a Dose Limiting Toxicity (DLT) by the end of the first treatment cycle (DLT)
研究概览
简要总结
Study has two parts:
- Dose-finding: to determine the maximum tolerated dose (MTD) and to evaluate the safety and tolerability of RAD001 (everolimus , Afinitor®) in combination with BEZ235 in patients with advanced solid tumors.
- Dose-expansion: to assess safety and tolerability of RAD001 and BEZ235 at the MTD in patients with ER+/HER2- metastatic breast cancer and metastatic renal cell cancer
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients age 18 years or older
- •In the dose finding phase, patients with histologically or cytologically confirmed advanced solid malignancies that are metastatic or unresectable
- •In the dose expansion phase, the enrollment will be limited to patients with:
- •Patients with metastatic renal cell carcinoma (mRCC) whose disease had progressed despite prior treatment with VEGFR-TKI (vascular endothelial growth factor receptor tyrosine kinase inhibitor) therapy (at least one but no more than two lines of VEGFR-TKI therapy) Patients with metastatic breast cancer (MBC) which is ER+/HER2-, whose disease had progressed despite prior treatment with at least one but no more than two lines of chemotherapy and at least one prior line of endocrine therapy in the metastatic setting
- •WHO performance status of 0-2
- •Lab parameters within specifically defined criteria
- •Patients with measurable disease per RECIST 1.0
排除标准
- •Patients who have previously received mTOR inhibitors or PI3K inhibitors
- •Patients with CNS metastases unless previously treated with surgery, whole-brain radiation or stereotactic radiosurgery plus the disease having been stable for at least 2 months without steroid use for at least 1 month prior to the first dose of RAD001 and BEZ
- •Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs.
- •Major surgery within 2 weeks prior to study enrollment
- •Patient taking anti-cancer drug concomitantly
- •Received radiation within 4 weeks prior to study enrollment (2 weeks if limited field radiation)
- •Receive chemotherapy 4 weeks prior to study enrollment
- •Received live attenuated vaccines within 1 week prior to study enrollment
- •History of HIV
- •Any other severe and/or uncontrolled medical condition
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
RAD001 + BEZ235
Patients will receive first dose of RAD001 at 2.5mg/5mg/10 mg weekly or 2.5mg/5mg daily in combination of BEZ235 at 50 mg/100 mg/200 mg/300 mg/400 mg twice a day. In the initial cohort of the dose finding phase, patients will receive a single 2.5 mg dose of RAD001 on Cycle 1 Day 1 and the combination therapy of RAD001 2.5 mg/week and BEZ235 200 mg bid starting on Cycle 1 Day 8. Dose escalation phase: patients will start RAD001 and BEZ235 on Cycle 1 Day 1 with both study drugs being administered at the center. Dose expansion phase: the first 15 patients enrolled at selected sites will take RAD001 as monotherapy from Day 1 to Day 7 (for PK sampling). The combination therapy of RAD001 and BEZ235 will start on Day 8. All remaining patients will receive the combination therapy of RAD001 and BEZ235 starting on Cycle 1 Day 1.
干预措施: RAD001 + BEZ235 (Drug)
结局指标
主要结局
Probability of a Dose Limiting Toxicity (DLT) by the end of the first treatment cycle (DLT)
时间窗: First treatment cycle (28 days)
The maximum tolerated dose (MTD) and the dose limiting toxicities during the first cycle of treatment
Incidence of DLT in patients by the end of the first treatment cycle in the co-administration of RAD001 and BEZ235
时间窗: First treatment cycle (28 days)
Frequency of DLTs during the first cycle of treatment
Number of participants with adverse events and serious adverse events.
时间窗: 12 months
Measured by abnormal safety laboratory parameters, changes in electrocardiograms (ECGs), changes in vital signs and changes in physical examination parameters.
次要结局
- Duration of response (DoR) according to local assessments by RECIST 1.0 for RCC and MBC in dose expansion phase(8 weeks)
- Time versus blood concentration profiles(First treatment cycle ( 28 days))
- Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR)) according to local assessments by RECIST 1.0 for renal cell carcinoma (RCC) and metastatic breast cancer (MBC) in dose expansion phase(8 weeks)
- Progresive Free Survival (PFS) according to local assessments by RECIST 1.0 for renal cell carcinoma (RCC) and metastatic breast cancer (MBC) in dose expansion phase(8 weeks)