A Randomized Phase II Study to Assess the Efficacy of Pemetrexed or Sunitinib (NSC # 736511) or Pemetrexed Plus Sunitinib in the Second-Line Treatment of Advanced Non-small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 130
- 试验地点
- 129
- 主要终点
- 18 Week Progression-free Survival (PFS) Rate
研究概览
简要总结
This randomized phase II trial studies pemetrexed disodium and sunitinib malate to compare how well they work when given alone or together as second-line therapy in treating patients with stage IIIB or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether pemetrexed disodium and sunitinib malate are more effective when given alone or together in treating non-small cell lung cancer.
详细描述
PRIMARY OBJECTIVES:
I. To estimate the 18 week progression-free survival rate of pemetrexed (pemetrexed disodium) alone (Arm I), sunitinib (sunitinib malate) alone (Arm II) and pemetrexed plus sunitinib (Arm III) in the second-line setting of advanced non-small cell lung cancer (NSCLC).
SECONDARY OBJECTIVES:
I. To compare the progression-free survival of the three arms. II. To estimate the response rate, duration of response, rate of stable disease, overall survival and to characterize the toxicity profiles of the three arms.
III. To estimate the response rate, duration of response, rate of stable disease, overall survival and toxicity of sunitinib in those patients on Arm I that receive this regimen in the third line 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
- 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
- •Histologic documentation: histologic or cytologic documentation of NSCLC
- •Stage: IIIB/IV with evidence of disease progression following first-line therapy
- •Tumor site: lung (non-small cell)
- •No cavitary lesions
- •Only one prior chemotherapy regimen in the first-line stage IIIB/IV setting is allowed; this could have been either a platinum- or non-platinum-based regimen
- •First-line therapy must be completed >= 28 days before registration
- •Prior adjuvant therapy is allowed provided the patient had one previous regimen in the advanced stage IIIB/IV setting
- •At least 28 days from prior major surgery and at least 14 days from any prior radiotherapy before registration
- •No prior inhibitors of VEGF receptor (VEGFR) (e.g., SU5416, SU6668, AZ6474, SU11248, PTK787, AZD2171, AEE-788, sorafenib); prior treatment with epidermal growth factor receptor (EGFR) inhibitors and bevacizumab is allowed, provided at least 4 weeks has elapsed
- •No prior pemetrexed
- •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 nonmeasurable 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 0-1
- •Pregnant or nursing mothers are not eligible for this study; patients in their child bearing years must have a baseline negative pregnancy test (in the case of females); males and females must practice appropriate contraceptive measures during the period of protocol therapy and for 6 months after completion of protocol therapy; appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives (Norplant), or double barrier method (diaphragm plus condom)
- •No ongoing cardiac dysrhythmias, atrial fibrillation, or history of corrected QT interval (QTc interval) > 500 msec (within 2 years prior to registration); the use of agents with proarrhythmic potential (e.g., quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, 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 symptomatic congestive heart failure within 12 months prior to entry 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 or hyperthyroidism 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 use of the following specific inhibitors and inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) is not permitted; the following inhibitors of CYP3A4 are prohibited within 7 days before 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
- •No symptomatic or untreated central nervous system (CNS) metastases; patients with 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 chronic daily treatment with aspirin (> 325 mg/day) or non-steroidal antiinflammatory agents known to inhibit platelet function; treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal) is not allowed
- •No pleural effusions or ascites that are detectable on physical exam
排除标准
- 未提供
研究组 & 干预措施
Arm I (pemetrexed)
Patients receive pemetrexed disodium 500 mg/m^2 IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive sunitinib malate as in Arm II as third-line therapy.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (pemetrexed)
Patients receive pemetrexed disodium 500 mg/m^2 IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive sunitinib malate as in Arm II as third-line therapy.
干预措施: Pemetrexed Disodium (Drug)
Arm II (sunitinib)
Patients receive sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive pemetrexed disodium as in Arm I as third-line therapy.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (sunitinib)
Patients receive sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive pemetrexed disodium as in Arm I as third-line therapy.
干预措施: Sunitinib Malate (Drug)
Arm III (pemetrexed and sunitinib)
Patients receive pemetrexed disodium 500 mg/m^2 IV over 10 minutes on day 1 and sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive third-line therapy at the discretion of the treating physician.
干预措施: Laboratory Biomarker Analysis (Other)
Arm III (pemetrexed and sunitinib)
Patients receive pemetrexed disodium 500 mg/m^2 IV over 10 minutes on day 1 and sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive third-line therapy at the discretion of the treating physician.
干预措施: Pemetrexed Disodium (Drug)
Arm III (pemetrexed and sunitinib)
Patients receive pemetrexed disodium 500 mg/m^2 IV over 10 minutes on day 1 and sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive third-line therapy at the discretion of the treating physician.
干预措施: Sunitinib Malate (Drug)
结局指标
主要结局
18 Week Progression-free Survival (PFS) Rate
时间窗: At 18 weeks
The 18 week progression-free survival rate was defined as the proportion of patients that were alive and progression-free 18 weeks after registration into the study. Disease progression was assessed per modified RECIST criteria, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, in either primary or nodal lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of new lesions. Kaplan-Meier estimate of 18-week progression-free survival was calculated.
次要结局
- PFS(Time from randomization to disease progression and death of any cause, whichever comes first (up to 3 years))
- Overall Response Rate(Duration of treatment (up to 3 years))
- Overall Survival (OS)(Time from randomization to death (up to 3 years))