Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 8 - LEE011 for Patients With CDK4/6 Pathway Activated Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 106
- 试验地点
- 61
- 主要终点
- Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments
研究概览
简要总结
The purpose of this signal seeking study was to determine whether treatment with LEE011 demonstrates sufficient efficacy in CDK4/6 pathway activated solid tumors and/or hematologic malignancies to warrant further study.
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
- •Patient had a confirmed diagnosis of a select solid tumor (except breast cancer (however, triple negative was included), liposarcoma, CRPC, melanoma and teratoma) or hematological malignancy (except mantle cell lymphoma).
- •Patient must have been pre-identified as having a tumor with CDK4 amplification or mutation, CDK6 amplification or mutation, Cyclin D1 (CCND1) amplification, Cyclin D3 (CCND3) amplification, or p16 (CDKN2A) mutation
- •Patient had received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission.
- •Patient had progressive and measurable disease as per RECIST 1.
- •or other appropriate hematological guidelines.
- •Patient had an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
排除标准
- •Patients had received prior treatment with LEE
- •Patient had clinically significant resting bradycardia (heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR interval > 220 msec, QRS interval > 109 msec, or QTcF > 450 msec.
- •Patients had primary CNS tumor or CNS tumor involvement
- •Patient had received chemotherapy or anticancer therapy ≤ 4 weeks prior to starting study drug
研究组 & 干预措施
LEE011
LEE011 600 mg (hard gelatin capsules) was administered orally once daily for 3 weeks on/1 week off. A complete treatment cycle was defined as 28 days.
干预措施: LEE011 (Drug)
结局指标
主要结局
Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments
时间窗: Baseline up ≥16 weeks up to approximately 36 months
Clinical benefit (CB) for patients with solid tumors were assessed using RECIST 1.1 and included responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) for ≥ 16 weeks. CR and PR (for solid tumors) required a confirmation at least 4 weeks after the initial response observation. For hematologic tumors other appropriate hematological response criteria was applied. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to \<10 mm, PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD=At least a 20% increase in the sum of diameter of all measured target lesions and also demonstrate an absolute increase of at least 5 mm. FAS
Clinical Benefit Rate (CBR) of ≥ 16 Weeks FAS
时间窗: Baseline and ≥ 16 weeks up to approximately 36 months
CBR was determined by local, Investigator assessment for each tumor assessment and defined as responses of CR + PR + SD for ≥ 16 weeks. CR and PR (for solid tumors) required a confirmation at least 4 weeks after the initial response observation. For hematologic tumors other appropriate hematological response criteria was applied. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to \<10 mm, PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD=At least a 20% increase in the sum of diameter of all measured target lesions and also demonstrate an absolute increase of at least 5 mm FAS
Overall Response Rate (ORR) ≥ 16 Weeks. FAS
时间窗: Baseline and ≥ 16 weeks up to approximately 36 months
ORR was determined by local, Investigator assessment for each tumor assessment and defined as responses of CR+PR ≥ 16 weeks. FAS
次要结局
- Progression Free Survival (PFS)(Every 8 weeks until death, assessed up to 24 months)
- Overall Survival (OS)(Baseline up to approximately 36 months)
- Number of Days for Duration of Response for Responders(Baseline up to approximately 36 months)