临床试验/NCT03052608

NCT03052608进行中（未招募）3 期

A PHASE 3, RANDOMIZED, OPEN-LABEL STUDY OF LORLATINIB (PF-06463922) MONOTHERAPY VERSUS CRIZOTINIB MONOTHERAPY IN THE FIRST-LINE TREATMENT OF PATIENTS WITH ADVANCED ALK-POSITIVE NON-SMALL CELL LUNG CANCER

Pfizer139 个研究点分布在 9 个国家目标入组 296 人开始时间: 2017年4月27日最近更新: 2025年11月25日

干预措施

试验速览

阶段: 3 期
状态: 进行中（未招募）
发起方: Pfizer
入组人数: 296
试验地点: 139
主要终点: Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) Assessment

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

A phase 3 study to demonstrate whether lorlatinib given as monotherapy is superior to crizotinib alone in prolonging the progression-free survival in advanced ALK-positive NSCLC patients who are treatment naïve and to compare lorlatinib to crizotinib with respect to overall survival in the same population

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 locally advanced or metastatic ALK-positive NSCLC; at least 1 extracranial measurable target lesion not previously irradiated. CNS metastases allowed if asymptomatic and not currently requiring corticosteroid treatment.
•Availability of an archival FFPE tissue specimen.
•No prior systemic NSCLC treatment.
•ECOG PS 0, 1, or
•Age ≥18 years .
•Adequate Bone Marrow, Liver, Renal, Pancreatic Function
•Negative pregnancy test for females of childbearing potential

排除标准

•Spinal cord compression unless good pain control attained
•Major surgery within 4 weeks prior to randomization.
•Radiation therapy within 2 weeks prior to randomization, including stereotactic or partial brain irradiation. Whole brain irradiation within 4 weeks prior to randomization
•Active bacterial, fungal, or viral infection
•Clinically significant cardiovascular disease, active or within 3 months prior to enrollment. Ongoing cardiac dysrhythmias, uncontrolled atrial fibrillation, bradycardia or congenital long QT syndrome
•Predisposing characteristics for acute pancreatitis in the last month prior to randomization.
•History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease
•Active malignancy (other than NSCLC, non melanoma skin cancer, in situ cervical cancer, papillary thyroid cancer, LCIS/DCIS of the breast, or localized prostate cancer) within the last 3 years prior to randomization.
•Concurrent use of any of the following food or drugs within 12 days prior to the first dose of lorlatinib or crizotinib.
•known strong CYP3A inhibitors .
•known strong CYP3A inducers
•known P gp substrates with a narrow therapeutic index
•Concurrent use of CYP3A substrates with narrow therapeutic indices within 12 days prior to the first dose of lorlatinib or crizotinib.
•Other severe acute or chronic medical or psychiatric condition, including recent or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or interfere with the interpretation of study results
•Investigational site staff members directly involved in the conduct of the study and their family members, or Pfizer employees, including their family members, directly involved in the conduct of the study.
•Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation.

研究组 & 干预措施

Lorlatinib

Experimental

Lorlatinib single agent, 100 mg (4 x 25 mg) oral tables, QD, continuously

干预措施: Lorlatinib (Drug)

Crizotinib

Active Comparator

Crizotinib single agent, 250 mg (1 x 250) oral capsules, BID, continuously

干预措施: Crizotinib (Drug)

结局指标

主要结局

Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) Assessment

时间窗: From time of Study Start up to 33 months

PFS was defined as the time from randomization to the date of the first documentation of progressive disease as assessed by the independent radiologist or death due to any cause, whichever occurred first. PFS (in months) was calculated as (date of event or censoring-randomization+1)/30.4375. Progressive disease is defined per RECIST version 1.1, as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.

次要结局

Overall Survival (OS)(From time of Study Start up to 33 months)
Progression-Free Survival (PFS) Based on Investigator's Assessment(From time of Study Start up to 33 months)
Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on BICR Assessment(From time of Study Start up to 33 months)
Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on Investigator's Assessment(From time of Study Start up to 33 months)
Intracranial Objective Response Rate (IC-ORR) - Percentage of Participants With Intracranial Objective Response (IC-OR) Based on BICR Assessment(From time of Study Start up to 33 months)
Intracranial Time to Progression (IC-TTP) Based on BICR Assessment(From time of Study Start up to 33 months)
Duration of Response (DR) Based on BICR Assessment(From time of Study Start up to 33 months)
Intracranial Duration of Response (IC-DR) Based on BICR Assessment(From time of Study Start up to 33 months)
Time to Tumor Response (TTR) Based on BICR Assessment(From time of Study Start up to 33 months)
Intracranial Time to Tumor Response (IC-TTR) Based on BICR Assessment(From time of Study Start up to 33 months)
PFS2 Based on Investigator's Assessment(From time of Study Start up to 45 months)
Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related)(From time of Study Start up to 33 months)
Number of Participants With Changes in Hematology Laboratory Parameters From Baseline Maximum NCI-CTCAE Grade Lower Than 3 to Postbaseline Maximum Grade 3 or Grade 4(From Baseline up to 33 months)
Number of Participants With Changes in Chemistry Laboratory Parameters From Baseline Maximum NCI-CTCAE Grade Lower Than 3 to Postbaseline Maximum Grade 3 or Grade 4(From Baseline up to 33 months)
Number of Participants With Changes in Lipid Laboratory Parameters From Baseline Maximum NCI-CTCAE Grade Lower Than 3 to Postbaseline Maximum Grade 3 or Grade 4(From Baseline up to 33 months)
Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria(From Baseline up to 33 months)
Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria(From Baseline up to 33 months)
Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Points in Left Ventricular Ejection Fraction (LVEF) Percentage(From Baseline up to 33 months)
Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time(Baseline, Cycle 2 Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C8D1, C10D1, C12D1, C14D1, C16D1, C18D1, C20D1, C22D1, C24D1, C26D1, C28D1, C30D1, C32D1, C34D1, C36D1, C38D1 and End of Treatment)
Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time(Baseline, Cycle 2 Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C8D1, C10D1, C12D1, C14D1, C16D1, C18D1, C20D1, C22D1, C24D1, C26D1, C28D1, C30D1, C32D1, C34D1, C36D1, C38D1 and End of Treatment)
Change From Baseline in Global Quality of Life (QOL), Functional Scales and Symptoms Scales as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) During Overall Treatment(From Baseline up to Cycle 38 Day 1)
Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment(From Baseline up to Cycle 38 Day 1)
Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time(Baseline, Day 1 of all cycles from Cycle 2 to Cycle 38, and End of Treatment)
Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time(Baseline, Day 1 of all cycles from Cycle 2 to Cycle 38, and End of Treatment)
Time to Deterioration (TTD) in Participant Reported Pain in Chest, Dyspnea, or Cough From QLQ-LC13(From Baseline up to 33 months)
Number of Participant With ALK Domain Mutation in Plasma Circulating Nucleic Acid (CNA) Analysis at Screening, Cycle 2 Day 1 and Cycle 7 Day 1(at Screening, Cycle 2 Day 1 and Cycle 7 Day 1)
Number of Participant With ALK Fusion Variant in Plasma Circulating Nucleic Acid (CNA) Analysis at Screening, Cycle 2 Day 1 and Cycle 7 Day 1(at Screening, Cycle 2 Day 1 and Cycle 7 Day 1)

研究者

发起方

Pfizer

申办方类型

Industry

责任方

Sponsor

研究点 (139)

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