NCT02838420已完成3 期
Randomized, Multicenter, Phase III, Open-Label Study of Alectinib Versus Crizotinib in Asian Patients With Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 187
- 试验地点
- 19
- 主要终点
- Progression-Free Survival (PFS) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumor (RECIST) v1.1
研究概览
简要总结
This randomized, multicenter, Phase III, open-label study will evaluate the efficacy and safety of alectinib versus crizotinib and to evaluate the pharmacokinetics of alectinib in asian participants with treatment-naive ALK-positive advanced NSCLC. Participants will be randomized 2:1 into one of the two treatment groups to receive either alectinib (600 milligrams [mg] twice daily [BID]) or crizotinib (250 mg BID) orally, respectively.
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 diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive as assessed by the Ventana immunohistochemistry (IHC) test. Sufficient tumor tissue available to perform ALK IHC is required. Ventana IHC testing will be performed at the designated central laboratory
- •Life expectancy of at least 12 weeks
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2
- •No history of receiving systemic treatment for advanced, recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC
- •Adequate hematologic function: Platelet count greater than equal to (>=) 100×10^9 per liter (/L); absolute neutrophil count (ANC) >=1500 cells per microliter (cells/mcL); hemoglobin>=9.0 grams per deciliter (g/dL)
- •Adequate renal function: an estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) formula of >=45 milliliters per minute per 1.73 square meter
- •Participants must have recovered from effects of any major surgery or significant traumatic injury at least 28 days before receiving the first dose of study treatment
- •Measurable disease (by Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1]) before administration of study treatment
- •Previous brain or leptomeningeal metastases are allowed if the participant is asymptomatic (e.g., diagnosed incidentally at study baseline). Asymptomatic central nervous system (CNS) lesions may be treated at the discretion of the investigator as per local clinical practice. If participant has neurological symptoms or signs because of CNS metastasis, the participant must complete whole-brain radiation or gamma knife irradiation treatment. In all cases, radiation treatment must be completed >=14 days before enrollment and disease must be clinically stable
- •For all females of childbearing potential, a negative serum pregnancy test result must be obtained within 3 days prior to starting study treatment
- •For women who are not postmenopausal (>=12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus), agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 3 months after the last dose of study drug. Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. Examples of contraceptive methods with a failure rate of <1% per year include tubal ligation, male sterilization, hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices. Alternatively, two methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of <1% per year. Barrier methods must always be supplemented with the use of a spermicide
- •For men, agreement to remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for at least 3 months after the last dose of study drug. Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception
排除标准
- •A malignancy within the previous 3 years (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal (GI) cancer by endoscopic resection, in situ carcinoma of the cervix, or any cured cancer that is considered to have no impact in progression-free survival (PFS) or overall survival (OS) for the current NSCLC)
- •Any GI disorder that may affect absorption of oral medications, such as malabsorption syndrome or status post-major bowel resection
- •Liver disease characterized by:
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than (>) 3× the upper limit of normal (ULN; >=5×ULN for participants with concurrent liver metastases) confirmed on two consecutive measurements; or
- •Impaired excretory function (e.g., hyperbilirubinemia), synthetic function, or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices; or
- •Acute viral or active autoimmune, alcoholic, or other types of hepatitis
- •National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 Grade 3 or higher toxicities because of any previous therapy (e.g., radiotherapy) (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication
- •History of organ transplant
- •Co-administration of anti-cancer therapies other than those administered in this study
- •Baseline QTc >470 ms or symptomatic bradycardia
- •Administration of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the receiving the first dose of study treatment and during treatment with alectinib or crizotinib
- •Administration of agents with potential QT interval prolonging effects within 14 days prior to receiving the first dose of study drug
- •History of hypersensitivity to any of the additives in the alectinib or crizotinib drug formulation
- •Pregnant or lactating
- •Known human immunodeficiency virus (HIV-positivity or acquired immunodeficiency syndrome (AIDS)-related illness
- •Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications or that would, in the opinion of the Principal Investigator, pose an unacceptable risk to the participant in this study
- •Any psychological, familial, sociological, or geographical condition that potentially hampers compliance with the study protocol requirements or follow-up procedures; those conditions should be discussed with the participant before study entry
研究组 & 干预措施
Crizotinib
Active Comparator
Participants will receive crizotinib capsules orally at a dose of 250 mg BID with or without food until disease progression, unacceptable toxicity withdrawal of consent, or death.
干预措施: Crizotinib (Drug)
Alectinib
Experimental
Participants will receive alectinib capsules orally at a dose of 600 mg BID with food until disease progression, unacceptable toxicity withdrawal of consent, or death.
干预措施: Alectinib (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumor (RECIST) v1.1
时间窗: From the date of randomization to the date of the first documented disease progression or death, whichever occurred first (up to overall period of approximately 40 months)
PFS was defined as the time (in months) from randomization to the first documentation of disease progression, as determined by the investigators, or to death from any cause, whichever occurred first.
Progression-Free Survival (PFS) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumor (RECIST) v1.1
时间窗: From the date of randomization to the date of the first documented disease progression or death, whichever occurred first (up to overall period of approximately 40 months)
PFS was defined as the time (in months) from randomization to the first documentation of disease progression, as determined by the investigators, or to death from any cause, whichever occurred first.
次要结局
- Overall Survival Time(Baseline, until death (up to overall period of approximately 40 months))
- Percentage of Participants With Non-serious Adverse Events and Serious Adverse Events(Up to overall period of approximately 40 months)
- Time to Deterioration Assessed Using EORTC Quality of Life Questionnaire-Core (QLQ-C30) Score(Baseline, Week 4, thereafter every 4 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months))
- Time to Deterioration Assessed Using EORTC Quality of Life Questionnaire-Lung Cancer Module (QLQ-LC13) Score(Baseline, Week 4, thereafter every 4 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months))
- Area Under the Plasma Concentration-time Curve (AUC) of Alectinib and Its Metabolite(Baseline and Week 4 predose (within 2 hours before administration of study drug))
- Maximum Plasma Concentration Observed (Cmax) of Alectinib and Its Metabolite(Baseline and Week 4 predose (within 2 hours before administration of study drug))
- Time to Cmax (Tmax) of Alectinib and Its Metabolite(Baseline and Week 4 predose (within 2 hours before administration of study drug))
- PFS as Determined by Independent Review Committee (IRC) Using RECIST v1.1(Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months))
- Percentage of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by Investigator Using RECIST v1.1(Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months))
- Time to Progression of Disease in the CNS as Determined by IRC Using RECIST v1.1(Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months))
- Time to Progression of Disease in the CNS as Determined by IRC Using Response Assessment in Neuro-Oncology (RANO)(Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months))
- Duration of Response (DOR) Assessed by Investigator Using RECIST v1.1(Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months))
- PFS as Determined by Independent Review Committee (IRC) Using RECIST v1.1(Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months))
- Percentage of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by Investigator Using RECIST v1.1(Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months))
- Time to Progression of Disease in the CNS as Determined by IRC Using RECIST v1.1(Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months))
- Time to Progression of Disease in the CNS as Determined by IRC Using Response Assessment in Neuro-Oncology (RANO)(Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months))
- Duration of Response (DOR) Assessed by Investigator Using RECIST v1.1(Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months))
- Overall Survival Time(Baseline, until death (up to overall period of approximately 40 months))
- Percentage of Participants With Non-serious Adverse Events and Serious Adverse Events(Up to overall period of approximately 40 months)
- Time to Deterioration Assessed Using EORTC Quality of Life Questionnaire-Core (QLQ-C30) Score(Baseline, Week 4, thereafter every 4 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months))
- Time to Deterioration Assessed Using EORTC Quality of Life Questionnaire-Lung Cancer Module (QLQ-LC13) Score(Baseline, Week 4, thereafter every 4 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months))
- Area Under the Plasma Concentration-time Curve (AUC) of Alectinib and Its Metabolite(Baseline and Week 4 predose (within 2 hours before administration of study drug))
- Maximum Plasma Concentration Observed (Cmax) of Alectinib and Its Metabolite(Baseline and Week 4 predose (within 2 hours before administration of study drug))
- Time to Cmax (Tmax) of Alectinib and Its Metabolite(Baseline and Week 4 predose (within 2 hours before administration of study drug))
研究者
研究点 (19)
Loading locations...
相似试验
终止
3 期
A Study of Atezolizumab Versus Observation as Adjuvant Therapy in Participants With High-Risk Muscle-Invasive Urothelial Carcinoma (UC) After Surgical ResectionCarcinoma, Transitional CellNCT02450331Hoffmann-La Roche809
进行中（未招募）
3 期
Study Of Comparing SAF-189s With Crizotinib In First Line ALK-Positive Advanced and Metastatic NSCLCALK-positiveSAF-189sNon-Small Cell Lung CancerNCT06569420Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.275
已完成
3 期
A Study to Investigate the Efficacy and Safety of Bendamustine Compared With Bendamustine+Obinutuzumab (GA101) in Participants With Rituximab-Refractory, Indolent Non-Hodgkin's Lymphoma (GADOLIN)Non-Hodgkin's LymphomaNCT01059630Genentech, Inc.413
进行中（未招募）
3 期
Study of Acalabrutinib Versus Chlorambucil Plus Rituximab in Adult Subjects With Previously Untreated Chronic Lymphocytic LeukemiaUntreated Chronic Lymphocytic LeukemiaNCT04075292AstraZeneca155
已完成
3 期
A Study of Atezolizumab in Combination With Carboplatin Plus (+) Nab-Paclitaxel Compared With Carboplatin+Nab-Paclitaxel in Participants With Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC)Carcinoma, Non-Squamous Non-Small Cell LungNCT02367781Hoffmann-La Roche723