Randomized, Phase III, Double-Blind Placebo-Controlled Trial of Sunitinib (NSC #736511) as Maintenance Therapy in Non-progressing Patients Following an Initial Four Cycles of Platinum-Based Combination Chemotherapy in Advanced, Stage IIIB / IV Non-small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 210
- 试验地点
- 484
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
This randomized phase III trial studies sunitinib malate to see how well it works when given as maintenance therapy (meaning it is approved for treatment after chemotherapy) in patients with stage IIIB-IV non-small cell lung cancer who have responded to prior treatment with combination chemotherapy. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking the growth of new blood vessels necessary for tumor growth. It is not yet known whether sunitinib malate is effective in helping tumors continue to shrink or stop growing.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the effect of sunitinib (sunitinib malate) compared to placebo on progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) patients who have had either stable or responding disease over the course of their initial 4 cycles of platinum-based therapy.
SECONDARY OBJECTIVES:
I. To evaluate the toxicity of sunitinib compared to placebo in the maintenance setting.
II. To evaluate the additional response rate as a result of sunitinib in this setting.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Histologic or cytologic documentation of primary non-small cell lung cancer
- •Stage IIIB or IV disease patients who are not candidates for combined modality therapy (chemoradiotherapy)
- •No evidence of symptomatic or untreated brain metastases, spinal cord compression, or carcinomatous meningitis; patients with central nervous system (CNS) metastases must be asymptomatic, must have received definitive therapy (>= 6 weeks since resection or >= 2 weeks since radiotherapy) for brain metastases, and be off steroids or on a stable dose for 2 weeks prior to registration
- •No cavitary lesions
- •Patients must have received one chemotherapy regimen for stage IIIB or IV NSCLC; the regimen must include four cycles of platinum-based doublet chemotherapy with or without bevacizumab (bevacizumab may not be given beyond the fourth cycle of chemotherapy); patients must have achieved a complete response, partial response, or stable disease to first-line chemotherapy and have no evidence of disease progression; patients will be registered 3-5 weeks following day 1 of cycle 4 of prior therapy
- •No prior adjuvant chemotherapy for stage I-III resected NSCLC or combined modality therapy for stage III NSCLC
- •No other primary therapy (including experimental therapy) for NSCLC; palliative radiation therapy must have been completed at least one week before planned start of protocol therapy
- •Patients must have measurable or non-measurable disease
- •Measurable disease: lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 2 cm with conventional techniques or as >= 1 cm with spiral computed tomography (CT) scan
- •Non-measurable disease: all other lesions, including small lesions (longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and truly non-measurable lesions; lesions that are considered non-measurable include the following:
- •Bone lesions
- •Leptomeningeal disease
- •Pleural/pericardial effusion
- •Lymphangitis cutis/pulmonis
- •Abdominal masses that are not confirmed and followed by imaging techniques
- •Cystic lesions
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Non-pregnant and non-nursing
- •No ongoing cardiac dysrhythmias, atrial fibrillation, or history of corrected QT (QTc) interval >= 500 msec (within 2 years prior to registration); the use of agents with proarrhythmic potential (e.g., quinidine, procainamide, disopyramide, sotalol, probucol, haloperidol, risperidone, indapamide, flecainide) is not recommended while on protocol therapy
- •Patients with class I New York Heart Association (NYHA) heart failure are eligible; patients with a history of class II NYHA heart failure are eligible, provided they meet at least one of the following criteria:
- •Patients with a history of class II heart failure who are asymptomatic on treatment
- •Patients with prior anthracycline exposure
- •Patients who have received central thoracic radiation that included the heart in the radiotherapy port
- •Patients with a history of class III or IV NYHA heart failure within 12 months prior to registration are not eligible
- •No myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft or stenting, cerebrovascular accident or transient ischemic attack within the last year
- •Patients with hypertension that cannot be controlled by medications (> 150/100 mmHg despite optimal medical therapy) are not eligible
- •Patients who require use of therapeutic anticoagulation for thromboembolic disease are not eligible; Note: low doses of coumadin (up to 2 mg daily) are permitted for prophylaxis of thrombosis
- •No history of venous thrombosis, pulmonary embolism, or hypercoagulopathy syndrome
- •No history of pulmonary hemorrhage, bleeding diathesis, or evidence of hemoptysis; patients with blood-tinged or blood-streaked sputum will be permitted on study if the hemoptysis amounts to less than 5 ml of blood per episode and less than 10 ml of blood per 24-hour period in the best estimate of the investigator
- •Patients with a history of hypothyroidism are eligible, provided they are currently euthyroid
- •None of the following within 28 days of beginning treatment: abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, serious or non-healing wound, ulcer, or bone fracture
- •The following inhibitors of cytochrome P450 3A4 (CYP3A4) are prohibited within 7 days before beginning and during treatment with sunitinib: azole antifungals (ketoconazole, itraconazole), diltiazem, clarithromycin, erythromycin, verapamil, delavirdine, and human immunodeficiency virus [HIV] protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir, nelfinavir); the following inducers of CYP3A4 are prohibited within 12 days before beginning and during treatment with sunitinib: rifampin, rifabutin, carbamazepine, phenobarbital, phenytoin, St. John?s Wort, efavirenz, tipranavir; other inhibitors and inducers of CYP3A4 may be used if necessary, but their use is discouraged
- •Patients unable to take oral medication are not eligible
- •Granulocytes >= 1,500/mcl
- •Platelet count >= 100,000/mcl
- •Total bilirubin =< 1.5 x upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)=< 2.5 x ULN; patients with liver metastases may have AST and ALT =< 5 x ULN; all other patients will have AST and ALT =< 2.5 x ULN
- •Creatinine =< 1.5 mg/dl
排除标准
- 未提供
研究组 & 干预措施
Arm I (sunitinib malate)
Patients receive sunitinib malate 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (sunitinib malate)
Patients receive sunitinib malate 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Arm II (placebo)
Patients receive placebo 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Placebo (Other)
Arm II (placebo)
Patients receive placebo 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Arm II (placebo)
Patients receive placebo 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (sunitinib malate)
Patients receive sunitinib malate 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Sunitinib Malate (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Time from randomization to disease progression and death of any cause, whichever comes first (up to 5 years)
Progression Free Survival (PFS) was defined as the time from randomization until disease progression or death, whichever occurs first. The median PFS with 95% CI was estimated using the Kaplan-Meier method. Progression is defined as in the primary outcome measure.
次要结局
- Overall Survival (OS)(Time from randomization to death (up to 5 years))
- Percentage of Deterioration in Symptom Progression at 3 Months Using the EORTC LC13 Dyspnea Subscale(At 3 months)
- Grade and Type of Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0(Duration of study (up to 5 years))
- Percentage of Deterioration in QOL at 3 Months Using the EORTC QLQ-C30 Global Health Subscale(At 3 months)
- Response Rate (RR)(Duration of treatment (up to 5 years))