A Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial Comparing CB-839 in Combination With Cabozantinib (CB-Cabo) vs. Placebo With Cabozantinib (Pbo-Cabo) in Patients With Advanced or Metastatic Renal Cell Carcinoma (RCC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 444
- 试验地点
- 132
- 主要终点
- Progression-Free Survival (PFS) as Assessed by the Independent Radiology Committee (IRC)
研究概览
简要总结
Tthe primary objective of this study is to compare blinded Independent Radiology Committee (IRC)-adjudicated progression free survival (PFS) of patients treated with CB-839 + cabozantinib (CB-Cabo) versus placebo + cabozantinib (Pbo-Cabo) for advanced or metastatic clear-cell RCC (ccRCC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants, care providers, investigators and outcomes assessors are blinded to treatment. Progression free survival (PFS) will be assessed by a blinded Independent Radiology Committee for the primary endpoint of the study.
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
- •Documented histological or cytological diagnosis of renal cell carcinoma with a clear-cell component
- •Adult patients
- •Karnofsky Performance Score (KPS) ≥ 70%
- •Measurable Disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
- •1-2 lines of prior therapy for advanced or metastatic renal cell carcinoma (RCC) including one anti-angiogenic therapy (any vascular endothelial growth factor [VEGF] pathway-targeted agent used either as monotherapy or as a component of a combination regimen) OR the combination regimen of nivolumab + ipilimumab
- •Adequate hepatic, renal, cardiac and hematologic function
排除标准
- •Prior treatment with cabozantinib (or other mesenchymal-epithelial transition [MET] inhibitor) or CB-839
- •Receipt of other anticancer therapy within 2-6 weeks, depending on the treatment
- •Untreated or active brain metastases or central nervous system cancer, as defined per protocol
- •Prior gastric surgery, small bowel resection, or other conditions that may impede adequate absorption of oral study drug
- •Known active infection with human immunodeficiency virus (HIV), Hepatitis B or C virus
- •Inability to discontinue proton-pump-inhibitor use before randomization
- •Patients who are pregnant or lactating
研究组 & 干预措施
Pbo-Cabo
Placebo twice daily (BID) + cabozantinib (60 mg once daily [QD]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or unacceptable toxicity, whichever occurred first.
干预措施: Cabozantinib (Drug)
Pbo-Cabo
Placebo twice daily (BID) + cabozantinib (60 mg once daily [QD]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or unacceptable toxicity, whichever occurred first.
干预措施: Placebo (Drug)
CB-Cabo
CB-839 800 mg BID + cabozantinib (60 mg QD) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per RECIST v1.1 or unacceptable toxicity, whichever occurred first.
干预措施: CB-839 (Drug)
CB-Cabo
CB-839 800 mg BID + cabozantinib (60 mg QD) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per RECIST v1.1 or unacceptable toxicity, whichever occurred first.
干预措施: Cabozantinib (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) as Assessed by the Independent Radiology Committee (IRC)
时间窗: Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for PFS was 22.14 months.
PFS is defined as the time from randomization to the occurrence of disease progression as assessed by the IRC using RECIST v1.1 or death from any cause, whichever occurs first. Subjects not experiencing disease progression or death at the time of analysis of PFS will be censored at the date of the last evaluable radiographic disease assessment. RECIST v1.1 criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (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.
次要结局
- Overall Survival (OS)(Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for OS was 25.86 months.)
- PFS as Assessed by the Investigator(Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for PFS was 22.64 months.)