NCT01313663终止2 期
A Randomized, Open-label, Phase II, 2-arm Multi-center Trial Comparing Maintenance Therapy With Pazopanib or Pemetrexed in Non-progressing Subjects With Metastatic Stage IVA and IVB Non-squamous Non-small Cell Lung Cancer (NSCLC) After Induction Therapy With Carboplatin + Pemetrexed or Cisplatin + Pemetrexed
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
This is a Phase II, randomized, open-label, multi-center study in advanced (Stage IVA and IVB subjects per the International Association for the Study of Lung Cancer (IASLC) 2009 Lung cancer staging schema) non-squamous NSCLC subjects comparing pazopanib relative to pemetrexed in the maintenance setting. Subjects should have completed 4-6 cycles of induction therapy with carboplatin + pemetrexed or cisplatin + pemetrexed and have had Stable Disease (SD), Partial Response (PR) or Complete Response (CR) as the best response to be enrolled into the study. The primary objective is to estimate the hazard ratio of progression free survival (PFS) in advanced NSCLC subjects given maintenance therapy of pazopanib (Arm A) relative to pemetrexed (Arm B). The secondary objectives are: overall survival, response rates, safety and tolerability. A total of approximately 200 subjects will be enrolled and randomized in a 1:1 ratio. Safety and efficacy assessments will be regularly performed on all subjects.
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.
- •Subjects must complete 4 to 6 cycles of chemotherapy with carboplatin + pemetrexed or cisplatin + pemetrexed and have had SD, PR or CR at the time of screening/enrolment as the best response.
- •Prior surgery and/or localized irradiation for NSCLC is permitted as long as it was a minimum of 4 weeks before entering the study. Subjects with recurrence after previous NSCLC that has been treated with surgery and adjuvant chemotherapy or a radio-chemotherapy regimen with curative intent are eligible, provided 1 year has passed since this treatment ended.
- •Histologically or cytologically confirmed diagnosis of predominantly non-squamous cell Stage IVA Wet (with cytology positive Malignant Pleural Effusion (MPE)) or Stage IVB (metastatic) NSCLC.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy of at least 12 weeks.
- •Must have measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST). A measurable lesion is defined as a lesion that can be accurately measured in at least one dimension with the longest diameter ≥ 20 mm using conventional techniques, or ≥ 10 mm with spiral computed tomography (CT) scan.
- •Able to swallow and retain oral medication.
- •Adequate organ system function.
- •Women of childbearing potential must have a negative pregnancy test within <= 7 days prior to administration or dispensing of study treatment and agree to use effective contraception.
- •Age ≥ 18 years of legal age of consent if different from 18 years.
排除标准
- •History of active or any other malignancy other than lung cancer in the 2 yrs prior to the first dose of study drug other than NSCLC. Exception: Subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
- •History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti- seizure medications for 4 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases.
- •Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
- •Active peptic ulcer disease
- •Known intraluminal metastatic lesion/s with risk of bleeding
- •Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation
- •History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment
- •Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
- •Malabsorption syndrome Major resection of the stomach or small bowel
- •Presence of uncontrolled infection.
- •Corrected QT interval (QTc) > 480 msecs using Bazett's formula
- •History of any one or more of the following cardiovascular conditions within the past 6 months:
- •Cardiac angioplasty or stenting Myocardial infarction Unstable angina Coronary artery bypass graft surgery Symptomatic peripheral vascular disease Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA).
- •Poorly controlled hypertension, defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of
- •Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Blood pressure (BP) must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP / DBP values from each BP assessment must be <140/90 mmHg in order for a subject to be eligible for the study.
- •History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti- coagulating agents for at least 6 weeks are eligible.
- •Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major).
- •Evidence of active bleeding or bleeding diathesis.
- •Recent hemoptysis (>=½ teaspoon of red blood within 8 weeks before first dose of study drug).
- •Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels (Note: tumor abutting the vessel is acceptable, but contiguous tumor and vessel is not; CT with contrast is strongly recommended to evaluate such lesions).
- •Any serious and/or unstable pre-existing medical, psychiatric, or other condition that would make the subject inappropriate for study participation including any serious condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
- •Use of any prohibited medication within the timeframes listed in the protocol.
- •Prior use of an investigational agent within 28 days or 5 half-lives, whichever is longer, prior the first dose of study drug.
- •Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 (except the value for hemoglobin; see Table 1) and/or that is progressing in severity, except alopecia.
- •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib and/or pemetrexed.
- •Inability to interrupt aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) 2 days before, the day of, and 2 days after the dose of pemetrexed. If a subject is taking an NSAID (COX-2 inhibitors included) or salicylate with a long half-life (e.g.
- •naproxen, piroxicam, diflusinal, nabumetone, rofecoxib, or celecoxib) it should not be taken 5 days before, the day of, and 2 days after the dose of pemetrexed.
- •Inability or unwillingness to take folic acid, vitamin B12 supplementation, or dexamethasone.
- •Have clinically significant third-space fluid collections (e.g., ascites or pleural effusions) that cannot be controlled by drainage or other procedures prior to Day 1, Cycle
- •Treatment with any of the following anti-cancer therapies:
- •radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib
研究组 & 干预措施
Pazopanib
Experimental
oral agent, administered at 800 mg daily (400 mg tablets x 2). Dose can be reduced, interrupted or discontinued due to adverse events or intolerance
干预措施: pazopanib (Drug)
Pemetrexed
Active Comparator
pemetrexed IV 500 mg/m2 once every 3 weeks
干预措施: pemetrexed (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: From randomization until the first documented sign of investigator-assessed disease progression or death, whichever occurred first (average of 10 study weeks)
PFS is defined as the interval between the date of randomization and the first documented sign of investigator-assessed (per Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1) disease progression (PD) or death, whichever occurs first. The date of documented PD is the date of lesion evaluation in the case of radiological PD and the date of symptomatic cancer progression in the case of symptomatic progression (radiological confirmation is required). PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started. If the participant received subsequent anti-cancer therapy prior to the date of documented progression or death, PFS was to be censored at the last adequate assessment (LAA) prior to the initiation of therapy. Otherwise, if the participant did not have a documented date of progression or death, PFS was to be censored at the date of the LAA.
次要结局
- Number of Participants With a Increase From Baseline in Bazett's QTc at the Indicated Time Points(Baseline; Week 6; Week 15; every 9 weeks in the first 6 months; every 12 weeks in the next 6 months; and, after 1 year, every 6 months (up to Study Week 55))
- Number of Participants With a Change From Baseline Grade to Grade 3 and 4 for the Indicated Clinical Laboratory Parameters(From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55))
- Number of Participants (Par.) With the Indicated Best Overall Response(From randomization until the time of the first documented evidence of a confirmed complete response (CR) or partial response (PR) (average of 10 weeks))
- Number of Participants With Any Non-serious On-therapy Adverse Event (AE: Occurring in >=5% Participants in Any Treatment Arm) and Serious Adverse Event (SAE)(From the time the first dose of study treatment was administered until 28 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (up to Study Week 55))
- Overall Survival(From randomization until disease progression or death (up to Study Week 78))
- Mean Daily Dose, as a Measure of Extent of Exposure(From the first day to the last day of treatment (average of 8 weeks))
- Number of Participants With Any On-therapy AE (Serious or Non-serious) Leading to Dose Reductions (DRs) or Interruptions/Delays in the Study(From the time the first dose of study treatment was administered until discontinuation of treatment (up to Study Week 55))
- Number of Participants With the Indicated Grade Changes From Baseline Grade in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk. Phos.), and Total Bilirubin (TB)(From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55))
- Time on Study Treatment (Pazopanib), as a Measure of Extent of Exposure(From the first day to the last day of treatment (average of 8 weeks))
- Mean Number of Pemetrexed Dosing Cycles, as a Measure of Extent of Exposure(From the time the first dose of study treatment was administered until discontinuation of the study or death (average of 16 weeks))
- Average Dose of Pemetrexed for All Cycles, as a Measure of Extent of Exposure(From the time the first dose of study treatment was administered until discontinuation of the study or death (average of 16 weeks))
- Number of Participants With Any AE (Serious or Non-serious) Leading to Withdrawal From Study Treatment(From the time the first dose of study treatment was administered until withdrawal from study treatment (up to Study Week 55))
- Number of Participants With the Indicated Changes From Baseline Value in Lactate Dehydrogenase (LDH)(From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55))
- Number of Participants With the Indicated Worst-case Change From Baseline in Blood Pressure(From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55))
研究者
研究点 (1)
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