临床试验/NCT02811861

NCT02811861

进行中（未招募）

3 期

A Multicenter, Open-label, Randomized, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib in Combination With Everolimus or Pembrolizumab Versus Sunitinib Alone in First-Line Treatment of Subjects With Advanced Renal Cell Carcinoma (CLEAR)

Eisai Inc.226 个研究点分布在 9 个国家目标入组 1,069 人2016年10月13日

适应症Renal Cell Carcinoma

干预措施Lenvatinib Everolimus Pembrolizumab Sunitinib

概览

阶段: 3 期
干预措施: Lenvatinib
疾病 / 适应症: Renal Cell Carcinoma
发起方: Eisai Inc.
入组人数: 1069
试验地点: 226
主要终点: Progression-free Survival (PFS) by Independent Imaging Review (IIR)
状态: 进行中（未招募）
最后更新: 2个月前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验相关资讯

概览

简要总结

The primary purpose of the study is to demonstrate that lenvatinib in combination with everolimus (Arm A) or pembrolizumab (Arm B) is superior compared to sunitinib alone (Arm C) in improving progression-free survival (PFS) (by independent imaging review [IIR] using Response Evaluation Criteria in Solid Tumors [RECIST 1.1]) as first-line treatment in participants with advanced renal cell carcinoma (RCC).

注册库

clinicaltrials.gov

开始日期

2016年10月13日

结束日期

2027年3月31日

最后更新

2个月前

研究类型

Interventional

研究设计

Parallel

性别

All

研究者

发起方

Eisai Inc.

责任方

Sponsor

入排标准

入选标准

•Histological or cytological confirmation of RCC with a clear-cell component (original tissue diagnosis of RCC is acceptable).
•Documented evidence of advanced RCC.
•At least 1 measurable target lesion according to RECIST 1.1 meeting the following criteria:
•Lymph node (LN) lesion that measures at least 1 dimension as greater than or equal to (\>=) 1.5 cm in the short axis
•Lymph node (LN) lesion that measures at least 1 dimension as greater than or equal to (\>=) 1.5 centimeter (cm) in the short axis
•Non-nodal lesion that measures greater than or equal to (\>=) 1.0 cm in the longest diameter
•The lesion is suitable for repeat measurement using computerized tomography/magnetic resonance imaging (CT/MRI). Lesions that have had external beam radiotherapy (EBRT) or locoregional therapy must show radiographic evidence of disease progression based on RECIST 1.1 to be deemed a target lesion.
•3.Karnofsky Performance Status (KPS) of \>=70 4.Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal (\<=) 150/90 millimeter of mercury (mmHg) at Screening and no change in antihypertensive medications within 1 week prior to Cycle 1/Day 1 (C1/D1) 5.Adequate renal function defined as creatinine \<=1.5\*upper limit of normal (ULN); or for participants with creatinine greater than (\>) 1.5\*ULN, the calculated creatinine clearance \>=30 milliliters per minute (mL/min) (per the Cockcroft-Gault formula) is acceptable.
•6.Adequate bone marrow function defined by:
•Absolute neutrophil count (ANC) \>=1500/cubic millimeter (mm\^3)

排除标准

•Participants who have received any systemic anticancer therapy for RCC, including anti-vascular endothelial growth factor (VEGF) therapy, or any systemic investigational anticancer agent. Prior adjuvant treatment with an investigational anticancer agent is not allowed unless the investigator can provide evidence of participant's randomization to placebo arm.
•Participants with central nervous system (CNS) metastases are not eligible, unless they have completed local therapy (example, whole brain radiation therapy (WBRT), surgery or radiosurgery) and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (example, radiologic) or symptoms of CNS metastases must be stable for at least 4 weeks before starting study treatment
•Active malignancy (except for RCC, definitively treated basal or squamous cell carcinoma of the skin, and carcinoma in-situ of the cervix or bladder) within the past 24 months. Participants with history of localized \& low risk prostate cancer are allowed in the study if they were treated with curative intent and there is no prostate specific antigen (PSA) recurrence within the past 5 years
•Prior radiation therapy within 21 days prior to start of study treatment with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks prior to study treatment start
•Participants who are using other investigational agents or who had received investigational drugs \<=4 weeks prior to study treatment start.
•Received a live vaccine within 30 days of planned start of study treatment (Cycle 1/Day 1). Examples of live vaccines include, but are not limited to, measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (example, FluMist®) are live attenuated vaccines and are not allowed.
•Participants with proteinuria \>1+ on urine dipstick testing will undergo 24-h urine collection for quantitative assessment of proteinuria. Participants with urine protein \>=1 g/24 h will be ineligible
•Fasting total cholesterol \>300 milligram per deciliter (mg/dL) (or ˃7.75 millimole per liter (mmol/L)) and/or fasting triglycerides level ˃2.5 x upper limit of normal (ULN). Note: these participants can be included after initiation or adjustment of lipid-lowering medication
•Uncontrolled diabetes as defined by fasting glucose \>1.5 times the ULN. Note: these participants can be included after initiation or adjustment of glucose-lowering medication
•Prolongation of corrected QT (QTc) interval to \>480 milliseconds (ms)

研究组 & 干预措施

Lenvatinib 18 mg plus Everolimus 5 mg

Lenvatinib 18 milligrams (mg) administered orally, once daily, plus everolimus 5 mg administered orally, once daily in each 21-day cycle.

干预措施: Lenvatinib

Lenvatinib 18 mg plus Everolimus 5 mg

Lenvatinib 18 milligrams (mg) administered orally, once daily, plus everolimus 5 mg administered orally, once daily in each 21-day cycle.

干预措施: Everolimus

Lenvatinib 20 mg plus Pembrolizumab 200 mg

Lenvatinib 20 mg administered orally, once daily, in each 21-day cycle plus pembrolizumab 200 mg administered intravenously (IV), every 3 weeks on Day 1 of each 21-day cycle.

干预措施: Lenvatinib

Lenvatinib 20 mg plus Pembrolizumab 200 mg

Lenvatinib 20 mg administered orally, once daily, in each 21-day cycle plus pembrolizumab 200 mg administered intravenously (IV), every 3 weeks on Day 1 of each 21-day cycle.

干预措施: Pembrolizumab

Sunitinib 50 mg

Sunitinib 50 mg administered orally, once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment in each 21-day cycle.

干预措施: Sunitinib

结局指标

主要结局

Progression-free Survival (PFS) by Independent Imaging Review (IIR)

时间窗: From the date of randomization to the date of the first documentation of PD or date of death, whichever occurred first or up to data cutoff date 28 Aug 2020 (up to approximately 46 months)

PFS assessed by IIR was defined as the time from the date of randomization to the date of the first documentation of progressive disease (PD) or death (whichever occurred first) using Response Evaluation Criteria in Solid Tumors (RECIST 1.1). PD was defined as at least a 20 percent (%) increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS was analyzed using Kaplan-Meier method.

次要结局

Objective Response Rate (ORR)(Up to approximately 69 months)
Overall Survival (OS)(Up to approximately 69 months)
Number of Participants With At Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Up to approximately 69 months)
Number of Participants Who Discontinued Treatment Due to Toxicity(Up to approximately 69 months)
Time to Treatment Failure Due to Toxicity(Up to approximately 69 months)
Health-Related Quality of Life (HRQoL) Assessed by Functional Assessment of Cancer Therapy Kidney Syndrome Index-Disease-Related Symptoms (FKSI-DRS) Scores(Up to approximately 69 months)
HRQoL Assessed by European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Score(Up to approximately 69 months)
HRQoL Assessed by European Quality of Life (EuroQol) Five-Dimensional, 3-Level (EQ-5D-3L) Score(Up to approximately 69 months)
PFS on Next-line of Therapy (PFS2)(Up to approximately 69 months)
PFS by Investigator Assessment(Up to approximately 69 months)
Model-predicted Clearance for Lenvatinib and Everolimus(Cycles 1 and 2 Day 1; 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 15: predose and 2-12 hours postdose; Cycles 3, 4, 5 and 6 Day 1: predose (Cycle length=21 days))
Area Under the Plasma Drug Concentration-time Curve (AUC) for Lenvatinib and Everolimus(Cycles 1 and 2 Day 1; 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 15: predose and 2-12 hours postdose; Cycles 3, 4, 5 and 6 Day 1: predose (Cycle length = 21 days)