NCT00903175已完成2 期
An Open-label, Multicenter Phase II Study to Compare the Efficacy and Safety of RAD001 as First-line Followed by Second-line Sunitinib Versus Sunitinib as First-line Followed by Second-line RAD001 in the Treatment of Patients With Metastatic Renal Cell Carcinoma.
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 471
- 试验地点
- 36
- 主要终点
- Progression Free Survival First-Line (PFS 1-L)
研究概览
简要总结
This study assessed the efficacy and safety of first-line RAD001 followed by second-line sunitinib versus the opposite sequence: first-line sunitinib followed by second-line RAD001 for the treatment of patients with MRCC.
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 advanced renal cell carcinoma.
- •Patients with at least one measurable lesion.
- •Patients with a Karnofsky Performance Status ≥70%.
- •Adequate bone marrow function.
- •Adequate liver function.
- •Adequate renal function.
- •Left ventricular ejection fraction (LVEF) ≥ lower limit of institutional normal (LLN)
- •Women of childbearing potential must have had a negative serum pregnancy test within 14 days prior to the administration of the study medication. Adequate contraception must be used while on study.
排除标准
- •Less than 4 weeks post-major surgery
- •Patients who had radiation therapy within 4 weeks prior to start of study treatment (palliative radiotherapy to bone lesions allowed within 2 weeks prior to study treatment start).
- •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 have previously received systemic mTOR inhibitors (sirolimus, temsirolimus, everolimus) or VEGF inhibitors. Note: History of adjuvant immunotherapy, vaccines or adjuvant sorafenib following localized surgical nephrectomy is acceptable.
- •Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins or to its excipients
- •Patients with a known hypersensitivity to sunitinib or its excipients
- •History or clinical evidence of central nervous system (CNS) metastases. Note: Subjects who have previously-treated CNS metastases (surgery plus or minus radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible:
- •Are asymptomatic and,
- •have had no evidence of active CNS metastases for ≥ 6 months prior to enrollment and,
- •have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC)
- •Clinically significant gastrointestinal abnormalities including, but not limited to:
- •Malabsorption syndrome
- •Major resection of the stomach or small bowel that could affect the absorption of study drug
- •Active peptic ulcer disease
- •Inflammatory bowel disease
- •Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation
- •History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
- •Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥160mmHg or diastolic blood pressure (DBP) of ≥ 95mmHg]
- •Patients receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent
- •Patients with a known history of HIV seropositivity.
- •Patients with active bleeding.
- •Patients who have any severe and/or uncontrolled medical conditions or other conditions within the past 12 months that could affect their participation in the study such as:
- •Cardiac angioplasty or stenting, unstable angina pectoris, symptomatic peripheral vascular disease, symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction ≤ 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia, cerebrovascular accidents ≤ 6 months before study treatment start.
- •Prolongation of corrected QT interval (QTc) > 500 milliseconds (msecs).
- •Severally impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 0^2 saturation that is 88% or less at rest on room air.
- •Poorly controlled diabetes as defined by fasting serum glucose >2.0 x ULN.
- •Any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study.
- •Liver disease such as chronic active hepatitis or chronic persistent hepatitis.
- •History of cerebrovascular accident (CVA) including transient ischemic attack (TIA).
- •History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.
- •Patients who have a history of another primary malignancy and off treatment for ≤ 3 years
- •Female patients of child-bearing potential who are not using adequate birth control methods, or who are pregnant or breast feeding.
- •Patients who are using other investigational agents or who had received investigational drugs ≤ 2 weeks prior to study treatment start.
- •Patients unwilling or unable to comply with the protocol.
研究组 & 干预措施
everolimus 1L/sunitinib 2L
Experimental
everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
干预措施: everolimus (Drug)
everolimus 1L/sunitinib 2L
Experimental
everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
干预措施: sunitinib (Drug)
sunitinib 1L/everolimus 2L
Active Comparator
sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
干预措施: everolimus (Drug)
sunitinib 1L/everolimus 2L
Active Comparator
sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
干预措施: sunitinib (Drug)
结局指标
主要结局
Progression Free Survival First-Line (PFS 1-L)
时间窗: based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to 35 months
PFS_1L based on investigator assessment of radiology data by RECIST 1.0, was defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause during or after first-line treatment with everolimus or sunitinib. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
次要结局
- Time to Definitive Deterioration of the FKSI-DRS Risk Score by at Least 3 Score Units by First and Second-line Drugs Combined(<=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months)
- Progression-free Survival Combined (PFS-C)(based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to about 56 months)
- Overall Survival (OS)(Every 2 months from randomization up to 3 years after last patient randomized)
- Time to Definitive Deterioration of the Global Health Status/QoL Scores of the EORTC QLQ-C30 by First and Second-Line Drugs Combined(<=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months)
- Overall Response Rate (ORR) - First -Line (1-L)(based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to 35 months)
- Duration of Response (DoR) - First-Line (1-L)(based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to 35 months)
- Time to Definitive Deterioration of the FKSI-DRS Risk Score by at Least 3 Score Units by First-line Drug(<=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months)
- Time to Definitive Deterioration of the Physical Functioning Scale of the EORTC QLQ-C30 - by First and Second-Line Drugs Combined(<=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months)
- Time to Definitive Deterioration of the Physical Functioning (PF) Scale of the EORTC QLQ-C30 - by First-Line (1L) Drug(<=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months)
- Time to Definitive Deterioration of the Global Health Status/QoL Scores of the EORTC QLQ-C30 by First-Line Drug(<=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months)
- Time to Definitive Deterioration of the Fatigue Scale of the EORTC QLQ-C30 by First-Line Drug(<=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months)
- Time to Definitive Deterioration of the Fatigue Scale of the EORTC QLQ-C30 by First and Second-Line Drugs Combined(<=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months)
研究者
研究点 (36)
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