A Randomized Phase II Trial of Weekly Topotecan With and Without AVE0005 (Aflibercept; NSC-724770) in Patients With Platinum Treated Extensive Stage Small Cell Lung Cancer (E-SCLC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 189
- 试验地点
- 257
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
This randomized phase II trial is studying topotecan to see how well it works when given with or without aflibercept in treating patients with extensive-stage small cell lung cancer. Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Combinations of biological substances in aflibercept may be able to carry tumor-killing substances directly to small cell lung cancer cells. Aflibercept may also stop the growth of small cell lung cancer by blocking blood flow to the tumor. It is not yet known whether topotecan is more effective with or without aflibercept in treating patients with small cell lung cancer.
详细描述
PRIMARY OBJECTIVES:
I. Evaluate the efficacy of topotecan hydrochloride with vs without aflibercept (ziv-aflibercept), in terms of progression-free survival at 3 months, in patients with extensive stage small cell lung cancer previously treated with platinum-based therapy.
SECONDARY OBEJCTIVES:
I. Assess the response rate (confirmed and unconfirmed, complete and partial responses) in a subset of patients with measurable disease.
II. Assess the overall survival of these patients. III. Evaluate the frequency and severity of toxicities of these regimens in these patients.
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
- •Histologically or cytologically confirmed extensive stage small cell lung cancer
- •Progressive or recurrent disease following one (and only one) standard first-line platinum-containing regimen (cisplatin or carboplatin)
- •Measurable or non-measurable disease per RECIST criteria
- •Disease must be outside a previously irradiated field OR a new lesion must be inside the irradiated field
- •Disease must be outside a previously resected area OR a new lesion must be present
- •No known brain metastasis unless the metastasis has been treated and is stable for ≥ 3 months prior to study entry
- •No leptomeningeal involvement or brain stem metastasis
- •Zubrod performance status 0-1
- •ANC ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Hemoglobin ≥ 10 g/dL
- •Serum creatinine ≤ 1.5 times upper limit of normal OR creatinine clearance ≥ 60 mL/min
- •Urine protein: creatinine ratio < 1 OR urine protein < 500 mg by 24-hour urine collection
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
- •Willing to provide smoking history
- •No evidence of active infection
- •No active bleeding
- •No significant history of bleeding diathesis, including hemoptysis (½ teaspoon of hemoptysis within the past 3 months), or underlying coagulopathy
- •No history of recent arterial embolic events, including any of the following:
- •Myocardial infarction
- •Cerebrovascular accident
- •Transient ischemic attack
- •Worsening of pre-existing angina within the past 6 months
- •No uncontrolled hypertension (systolic BP > 150 mm Hg or diastolic BP > 100 mm Hg)
- •History of hypertension allowed provided it is controlled on anti-hypertensive medications
- •No history of congestive heart failure
- •No history of encephalitis or encephalopathy of any cause
- •No diverticulitis, gastrointestinal bleeding, or peptic ulcer within the past 3 months
- •No known AIDS or HIV-1 associated complex
- •No known history of immune or immunodeficiency disorders
- •No unstable or pre-existing major medical conditions except for cancer-related abnormalities
- •No other prior malignancy except for any of the following:
- •Adequately treated basal cell or squamous cell skin cancer
- •In situ cervical cancer
- •Adequately treated stage I or II cancer currently in complete remission
- •Any other cancer from which the patient been disease-free for 5 years
- •Concurrent chronic therapeutic doses of low molecular weight heparin allowed
- •At least 21 days since prior and no concurrent radiotherapy and recovered
- •At least 28 days since prior and no concurrent surgery (e.g., thoracic or other major surgeries) and recovered
- •No prior bevacizumab or other anti-angiogenic therapies including, but not limited to, small molecule tyrosine kinase inhibitors
- •No concurrent enzyme-inducing anticonvulsant drugs
- •Non-enzyme-inducing anticonvulsant drugs (e.g., Keppra) allowed
- •Concurrent chronic oral anticoagulation therapy allowed provided INR is maintained in the therapeutic range (INR 2-3)
排除标准
- 未提供
研究组 & 干预措施
Arm I (ziv-aflibercept, topotecan hydrochloride)
Patients receive ziv-aflibercept IV over 1 hour on day 1 and topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responsive or stable disease after 4 courses may then receive ziv-aflibercept IV on day 1 and topotecan hydrochloride IV on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: ziv-aflibercept (Biological)
Arm I (ziv-aflibercept, topotecan hydrochloride)
Patients receive ziv-aflibercept IV over 1 hour on day 1 and topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responsive or stable disease after 4 courses may then receive ziv-aflibercept IV on day 1 and topotecan hydrochloride IV on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: topotecan hydrochloride (Drug)
Arm II (topotecan hydrochloride)
Patients receive topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responsive or stable disease after 4 courses may then receive topotecan hydrochloride IV on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: topotecan hydrochloride (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: Disease assessments were performed every 6 weeks, up to 2 years.
From the date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Progression is defined as 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration.
次要结局
- Response Rate (Confirmed and Unconfirmed, Complete and Partial Responses)(Disease assessment for response were performed every 6 weeks, up to 2 years.)
- Overall Survival(Weekly, up to 2 years.)
- Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drugs(Toxicity assessment was evaluated after each cycle (21 days), up to 2 years.)