A Randomized, Open-label, Multi-center Phase II Study to Compare Bevacizumab Plus RAD001 Versus Interferon Alfa-2a Plus Bevacizumab for the First-line Treatment of Patients With Metastatic Clear Cell Carcinoma of the Kidney
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 365
- 试验地点
- 10
- 主要终点
- Progression-free Survival (PFS) of Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab
研究概览
简要总结
To estimate the difference in efficacy and safety of bevacizumab and RAD001 compared to bevacizumab and interferon alfa-2a for first-line treatment of patients with metastatic carcinoma of the kidney.
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
- 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
- •Patients with metastatic renal cell carcinoma
- •Patients with at least one measurable lesion
- •Patients with progressive metastatic renal cell carcinoma
- •Patients who had a prior partial or complete nephrectomy
- •Patients with a Karnofsky Performance Status ≥70%.
- •Adequate bone marrow function
- •Adequate liver function
- •Adequate renal function
- •Adequate coagulation profile
排除标准
- •4 weeks post-major surgery
- •Patients who had radiation therapy within 28 days prior to start of study
- •Patients in need for major surgical procedure during the course of the study.
- •Patients with a serious non-healing wound, ulcer, or bone fracture.
- •Patients with a history of seizure(s) not controlled with standard medical therapy.
- •Patients who have received prior systemic treatment for their metastatic RCC.
- •Patients who received prior therapy with VEGF pathway inhibitor
- •Patients who have previously received systemic mTOR inhibitors
- •Patients with a known hypersensitivity RAD001 (everolimus) or other rapamycins or to its excipients.
- •Patients with history or current central nervous system (CNS) metastases or spinal cord compression.
- •Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.
- •Patients with proteinuria at screening.
- •Patients with inadequately controlled hypertension
- •Patients receiving ongoing or with recent need for full therapeutic dose of oral or parenteral anticoagulants or chronic daily treatment with aspirin
- •Patients receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent.
- •Patients with a known history of HIV
- •Patients with hypersensitivity to interferon alfa-2a or any component of the product.
- •Patients with an active, bleeding diathesis or coagulopathy or recurrent thromboembolism
- •Patients who have any severe and/or uncontrolled medical conditions or other conditions
- •Left Ventricular Ejection Fraction < lower limit of institutional normal assessed by ECHO or MUGA
- •Patients who have a history of another primary malignancy ≤ 3 years
- •Female patients who are pregnant or breast feeding
- •Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to study treatment start.
- •Patients unwilling to or unable to comply with the protocol
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
bevacizumab, RAD001 (everolimus)
Participants received oral everolimus 10 mg qd plus intravenous bevacizumab 10mg/kg every 2 weeks
干预措施: RAD001(everolimus) (Drug)
bevacizumab, RAD001 (everolimus)
Participants received oral everolimus 10 mg qd plus intravenous bevacizumab 10mg/kg every 2 weeks
干预措施: bevacizumab (Drug)
bevacizumab, interferon alfa-2a (IFN)
Participants received subcutaneous IFN dose escalated from 3 MIU (million international unit) during week 1, 6 MIU during week 2, and 9 MIU during week 3 of treatment and subsequently (if tolerated), 3 times per week plus intravenous bevacizumab 10 mg/kg every 2 weeks
干预措施: interferon alfa-2a (Drug)
bevacizumab, interferon alfa-2a (IFN)
Participants received subcutaneous IFN dose escalated from 3 MIU (million international unit) during week 1, 6 MIU during week 2, and 9 MIU during week 3 of treatment and subsequently (if tolerated), 3 times per week plus intravenous bevacizumab 10 mg/kg every 2 weeks
干预措施: bevacizumab (Drug)
结局指标
主要结局
Progression-free Survival (PFS) of Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab
时间窗: Time from randomization to the date of radiological progressive disease as per independent central review, death from any cause, or last tumor assessment, reported between date of first participant randomized until 31Dec2011, cutoff date.
Tumor response and disease progression were assessed using response evaluation criteria in solid tumors (RECIST), version 1.0. All target and non-target lesions identified at baseline were assessed using the same method, CT scan with contrast or MRI with contrast, throughout the trial. All scans were reviewed by independent, central radiology. Disease progression was defined as: 1) a 20% increase in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of the longest diameters of all target lesions recorded at or after baseline or 2) the appearance of a new lesions or 3) the unequivocal progression of non-target lesions overall.
次要结局
- Time to Definitive Deterioration of the Functional Assessment of Cancer Therapy Kidney Symptom Index, Disease Related Symptoms (FKSI-DRS) Risk Score by at Least 2 Score Units(Time from randomization to the date of definitive deterioration (defined as no later increase above the threshold observed during the study), or date of last assessment, reported between date of first patient randomized until 31Dec2011)
- Overall Survival (OS) Treatment Effect in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab(Time from randomization to the date of death from any cause, reported between date of first participant randomized and up to 2 years after the last participant randomized (data cutoff: 30Aug2012))
- Duration of Exposure of RAD001 in Participants Randomized to the Treatment Combination of RAD001 and Bevacizumab(From the date of the first participant treated until the last patient discontinued the study treatment + 28 days)
- Response Duration Differences in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab(Time from first documented response date of radiological progressive disease as per independent central review, death due to underlying cancer, or last tumor assessment, reported between date of first participant randomized until 31Dec2011, cut-off date.)
- Best Overall Response in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab(Time from first participant randomized until 31Dec2011, cutoff date.)
- Number of Participants Who Experienced Adverse Events (AEs), Serious Adverse Events and Deaths(From the first participant randomized until the last patient discontinued the study treatment + 28 days)
- Time to Definitive Deterioration of the Global Health Status and the Physical Functioning (PF) Subscale Scores of the European Organization for the Research and Treatment of Cancer (EORTC)-Core Quality of Life Questionnaire (QLQ-C30) by at Least 10%(Time from randomization to the date of definitive deterioration (defined as no later increase above the threshold observed during the study), or date of last assessment, reported between date of first participant randomized until 31Dec2011)