NCT01274273Unknown2 期
A Randomized Phase II Trial of IL-2/IFN-α Plus Bevacizumab Versus IL-2/IFN-α in Metastatic Renal Cell Carcinoma (mRCC) - Danish Renal Cancer Group (DARENCA) Study-1
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 入组人数
- 118
- 试验地点
- 2
- 主要终点
- Progression free survival, PFS
研究概览
简要总结
The purpose of this study is to determine whether interleukin-2, interferon-alpha in combination with bevacizumab are effective in the treatment of metastatic renal cell carcinoma (mRCC).
详细描述
Bevacizumab as monotherapy has effect in metastatic renal cell carcinoma (mRCC). Bevacizumab in combination with interferon-alfa (IFN-α) has significant efficacy in mRCC and has been approved by EMA and FDA.
The present study will assess whether the combination of Interleukin-2 (IL-2) and IFN-α with bevacizumab may add efficacy in patients with mRCC with a tolerable safety profile.
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
- •Signed written informed consent
- •Patient must be willing and able to comply with the protocol.
- •Age ≥ 18 years.
- •Histologic og cytologic biopsy proven locally advanced or metastatic renal cell carcinoma, considered non-candidates for curative surgery. Nephrectomy is not mandatory.
- •Patient with renal cell carcinoma (RCC) with a clear-cell histologic component confirmed by local pathology review.
- •Females with a negative serum pregnancy test unless childbearing potential can be otherwise excluded
- •Fertile women of childbearing potential (<2 years after last menstruation) and men must use effective means of contraception
- •Memorial-Sloan-Kettering-Cancer-Centre favourable- and intermediate prognostic group.
- •Measurable or non-measurable disease (as per RECIST1.1 criteria)
- •Karnofsky Performance status of 70% or higher.
- •Life expectancy greater than 4 months.
- •The required laboratory values at baseline are as follows:
- •Haematology:
- •WCC ≥ 3.0 x 109/L, Platelet count ≥ 100 x 109/L, Haemoglobin ≥ 6.2 mmol/l, (INR) ≤ 1.5, APTT ≤ 1.5 x ULN
- •Biochemistry:
- •Total bilirubin ≤ 1.5 x upper limit of normal (ULN), AST, ALT ≤ 2.5 x ULN in patients without liver metastases, ≤ 5 x ULN in patients with liver metastases, Serum Creatinine ≤ 150 micromol/L
排除标准
- •Prior systemic treatment for metastatic RCC disease
- •Major surgical procedure, open surgical biopsy, or significant traumatic injury within 28 days prior to randomization.
- •Serious non-healing wound, ulcer or bone fracture.
- •Evidence of current central nervous system (CNS) metastases or spinal cord compression. Patient must undergo an MRI or CT scan of the brain (with contrast, if possible) within 28 days prior to randomization.
- •Seizure(s) not controlled with standard medical therapy.
- •Dipstick urine test of protein ≥ 2+.
- •Other malignancies within 5 years prior to randomization (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix).
- •Evidence of bleeding diathesis or coagulopathy.
- •Ongoing or recent (within 10 days prior to study treatment start) need for full therapeutic dose of oral anticoagulants or chronic daily treatment with aspirin. Low molecular weight heparin are allowed
- •Uncontrolled hypertension (≥ 160 mm Hg systolic and/or ≥ 100 mm Hg diastolic) while receiving chronic medication.
- •Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents (≤ 6 months before randomisation), myocardial infarction (≤ 6 months before randomisation), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication.
- •Recent (within the 30 days prior to randomization) treatment with another investigational drug or participation in another investigational study.
- •Chronic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisolone equivalent), excluding inhaled steroids.
- •History or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk from treatment complications.
- •Known hypersensitivity to interleukin-2, Interferon, alfa or bevacizumab.
- •Serial blood test, serial tumor biopsies and serial dynamic contrast-enhanced imaging will be obtained as part of a translational research program integrated in the clinical trial.
- •Part(s) of the translational research program may be omitted in the individual patient due to practical, technical or safety reasons, without having consequences for participating in the additional translational research investigations or the clinical part of the study.
研究组 & 干预措施
Interleukin-2, interferon, bevacizumab
Experimental
干预措施: Bevacizumab (Drug)
Interleukin-2 and interferon-alfa
Active Comparator
干预措施: Interleukin-2 (Drug)
Interleukin-2 and interferon-alfa
Active Comparator
干预措施: Interferon Alfa-2b (Drug)
结局指标
主要结局
Progression free survival, PFS
时间窗: This is defined as the time between date of randomisation and the first date of documented disease progression or date of death due to any cause.
次要结局
- Frequency of surgical resection of residual disease(see below)
- Overall survival, (OS)(Overall survival is defined as the time between date of randomisation and the date of death due to any cause.)
- Time to treatment failure, (TTTF)(see below)
- Tolerability(see below)
- To explore the immunomodulatory effect of therapy in serial blood samples and serial tumor core biopsies and to correlate these biomarkers with outcome(see below)
- Response rate, RR(Overall response rate as assessed by the RECIST 1.1 criteria. An overall response is defined as a confirmed complete response (CR) or confirmed partial response (PR).)
- Duration of response(Duration of response is defined as the time between the date a response (CR or PR) was first seen until date of progression.)
- Time to progression, (TTP)(Time to progression is defined as time between date of randomisation and date of documented progression.)
- Frequency of no evidence of disease (NED)(see below)
- To assess dynamic contrast-enhanced imaging as a potential biomarker.(see below)
研究者
研究点 (2)
Loading locations...
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