A Phase II, Multicentre, Open-label Study of Cabozantinib as 2nd Line Treatment in Subjects With Unresectable, Locally Advanced or Metastatic Renal Cell Carcinoma With a Clear-Cell Component Who Progressed After 1st Line Treatment With Checkpoint Inhibitors.
概览
- 阶段
- 2 期
- 干预措施
- Cabozantinib
- 疾病 / 适应症
- Locally Advanced or Metastatic Renal Cell Carcinoma
- 发起方
- Ipsen
- 入组人数
- 127
- 试验地点
- 78
- 主要终点
- Cohort A: Objective Response Rate (ORR) Assessed by Independent Central Review
- 状态
- 已完成
- 最后更新
- 上个月
概览
简要总结
The overall objective of this study is to evaluate the efficacy and safety of cabozantinib as 2nd line treatment in subjects with unresectable, locally advanced or metastatic RCC with a clear-cell component, who progressed after prior Checkpoint Inhibitors (CPI) therapy with ipilimumab and nivolumab in combination or CPI combined with Vascular Endothelial Growth Factor (VEGF)-targeted therapy.
研究者
入排标准
入选标准
- •All subjects must fulfil all the following criteria to be included in the study:
- •Subjects must provide a signed informed consent prior to any study-related procedures;
- •Male or female subjects must be aged ≥18 years on the day the informed consent is signed;
- •Subjects must have histologically confirmed unresectable, locally advanced (defined as disease not eligible for curative surgery or radiation therapy) or metastatic RCC with a clear-cell carcinoma component;
- •Subjects must have radiographic disease progression, according to Investigator's judgement following 1st line treatment with CPI (ipilimumab plus nivolumab) (Cohort A) or CPI in combination with VEGF-targeted therapy (Cohort B);
- •Subjects present ≥1 target lesion according to RECIST 1.1 per Investigator;
- •Subjects should have Eastern Cooperative Oncology Group (ECOG) status 0-1;
- •Subjects with treated brain metastases are eligible if metastases have been shown to be stable as per Investigator's judgement;
- •Subjects must have adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 15 days before baseline:
- •Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L).
排除标准
- •Subjects will not be included in the study if the subject:
- •Inability to swallow tablets;
- •Was treated with any other investigational medicinal product (IMP) within the last 30 days before baseline;
- •Was previously treated with cabozantinib;
- •Has a contraindication to Magnetic Resonance Imaging (MRI) or contrast medium used for Contrast Tomography (CT)-scan;
- •Presents untreated brain or leptomeningeal metastases, or current clinical or radiographic progression of known brain metastases;
- •Has a diagnosis of a serious cardiovascular disorder:
- •Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, or serious cardiac arrhythmias;
- •Uncontrolled hypertension, defined as sustained blood pressure (BP) (\>140 mm Hg systolic or \>90 mm Hg diastolic pressure) despite optimal antihypertensive treatment;
- •Stroke (including transient ischaemic attack (TIA)), myocardial infarction (MI) or other ischaemic event, or thromboembolic event (e.g. deep venous thrombosis, pulmonary embolism) within 6 months before screening;
研究组 & 干预措施
Cohort A
Subjects who radiographically progressed after one prior line by CPI therapy with ipilimumab and nivolumab.
干预措施: Cabozantinib
Cohort B
Subjects who radiographically progressed after one prior line by CPI therapy combined with VEGF-targeted therapy.
干预措施: Cabozantinib
结局指标
主要结局
Cohort A: Objective Response Rate (ORR) Assessed by Independent Central Review
时间窗: Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months
ORR was defined as the percentage of participants who achieved a partial response (PR) or complete response (CR) at any timepoint as determined by independent central review per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. The confidence interval of the ORR was calculated using Clopper-Pearson exact method.
次要结局
- Time to Response (TTR) Assessed by Independent Central Review and Investigator(Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months)
- Duration of Response (DOR) Assessed by Independent Central Review and Investigator(Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months)
- Disease Control Rate (DCR) Assessed by Independent Central Review and Investigator(Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months)
- Progression-free Survival (PFS) Assessed by Independent Central Review and Investigator(Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months)
- Cohort B: Objective Response Rate Assessed by Independent Central Review(Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months)
- Objective Response Rate Assessed by Investigator(Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months)
- Overall Survival (OS) Assessed by Investigator(From the start of study treatment (Day 1) up to end of study, 45 months)
- Change From Baseline in Functional Assessment of Cancer Therapy-Kidney Cancer Symptom Index (FKSI-DRS) Score at Month 40(Baseline (Day 1) and Month 40)