Phase I/II Combined Alternating Sunitinib and Bevacizumab (Avastin®) in Advanced Renal Cell Carcinoma (CASA)
试验速览
- 阶段
- 1 期
- 入组人数
- 77
- 试验地点
- 1
- 主要终点
- Bevacizumab maximum tolerated dose, in combination with sunitinib
研究概览
简要总结
Combined sunitinib and bevacizumab in advanced renal cell carcinoma.
详细描述
This is a phase I/II trial of combined sunitinib and bevacizumab in advanced renal cell carcinoma ( CASBA) where Bevacizumab will be used only on day 29 of each 6 weeks sunitinib cycle.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed renal cell carcinoma with clear cell histology ( mixed histology with clear cell component is accepted)
- •Patient should have either locally advanced or metastatic disease
- •No prior anti-cancer therapy
- •Age ≥ 18 years
- •Life expectancy of 3 months or more
- •Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1
- •Performance status 0-2 by ECOG scale
- •Patients with controlled brain metastasis are accepted
- •Adequate renal function: serum creatinine ≤ 2 times the institutional upper limit of normal
- •Adequate hepatic function: total bilirubin within normal institutional limits, serum AST and ALT levels ≤2 times the institutional upper limit of normal or ≤ 5 times the institutional upper limit of normal of elevated because of liver involvement
- •Coagulation (PT ≤ 1.5 times the institutional upper limit of normal)
- •Adequate hematological values: leukocyte count ≥3.0 x 109/L, an absolute neutrophil count ≥1.5 x 109/L, a platelet count ≥100 x 109/L and hemoglobin ≥ 9.0 g/dL
- •Urine dipstick for proteinuria <1+, patients discovered to have ≥ 1+ on dipstick urinanalysis at baseline should have urine protein/urine creatinine ratio ≤1
- •Singed written informed consent before enrolment
- •Patient should have unresectable disease ( for both the primary tumor and the metastasis)
排除标准
- •Inability to comply with the protocol therapy
- •Uncontrolled hypertension defined as BP more than 160 systolic and or more than 100 diastolic despite adequate treatment at the time of treatment initiation.
- •Severe cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, myocardial infarction, significant arrhythmias or Transient ischemic attack (TIA) or cerebrovascular accident (CVA) in the last 6 months
- •Major bleeding disorder, significant traumatic injury or recent major surgery within 28 days of starting therapy. Or minor surgery (FNA/Core biopsy) within 7 days of starting therapy
- •History of abdominal abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months
- •Pre-existing thyroid abnormality
- •Concurrent proarrhythmic medications including terfenadine, quinidine, procainamide, disopyramide, sotalol, bepridil, haloperidol, risperidone, indapamide and flecainide
- •Recent significant hemoptysis (1/2 tea spoon red blood within last month)
- •Concurrent medication that either CYP 450 3A4 inducers or inhibitors
- •Concurrent use of proarrhythmic medications including terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide and flecainide
- •Pregnancy or breast feeding, or patient refusal to use appropriate contraception for female patients in childbirth age
- •Previous malignancy within 5 years, except adequately treated non melanomatous skin cancer or in situ cervical cancer
- •Psychiatric or mental disorder, precluding understanding of the information of the trial related topics and giving valid informed consent
- •Any psychological, familial, geographic or social circumstances which could impair the patient ability to participate in the trial and comply with follow up.
- •Any circumstance which might impair the patient's ability to comply with an out-patient regimen
- •Active uncontrolled infection
- •Serious underlying medical condition (in the judgment of the investigator) which could impair the ability of the patient to participate in the trial
- •Treatment with other experimental drugs within 30 days of entry into the trial
- •Treatment with other anti-cancer therapy
- •Legal incapacity
- •Significant proteinuria (urine protein: creatinine ratio > 1.0)
研究组 & 干预措施
Sunitinib and Bevacizumab Arm
Phase I/II Combined Alternating Sunitinib and Bevacizumab (Avastin®) in Advanced Renal Cell carcinoma (CASA)Combined Alternating Sunitinib and Bevacizumab
干预措施: Sunitinib (Drug)
Sunitinib and Bevacizumab Arm
Phase I/II Combined Alternating Sunitinib and Bevacizumab (Avastin®) in Advanced Renal Cell carcinoma (CASA)Combined Alternating Sunitinib and Bevacizumab
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Bevacizumab maximum tolerated dose, in combination with sunitinib
时间窗: 12 weeks from enrolling patient # 6
This is the phase I part of the study. patient will enroll on Bevacizumab dose of 5 mg/kg body weight. If no dose limiting toxicity in 1st 6 patients, the dose will be escalated to 10 mg/kg in the remainder of the patients
Assess response rate to the combination of sunitinib and bevacizumab
时间窗: Through study completion, an average of 6 months
response rate is the combination of partial response and complete response
Assess the progression free survival on the combination of sunitinib and bevacizumab
时间窗: up to 5 years
Progression free survival will be calculated from time of starting therapy till progression or death whichever comes first
次要结局
- Overall survival of patients in this regimen(Participants will be followed for the duration of hospital stay, up to 5 years)
- Number of participants with treatment related-adverse effects as assessed by CTCAE v 4.03(up to 5 years)