Clinical trial NCT01639001: A Study Of Crizotinib Versus Chemotherapy In Previously Untreated ALK Positive East Asian Non-Small Cell Lung Cancer Patients
Official title: PHASE 3, RANDOMIZED, OPEN-LABEL STUDY OF THE EFFICACY AND SAFETY OF CRIZOTINIB VERSUS PEMETREXED/CISPLATIN OR PEMETREXED/CARBOPLATIN IN PREVIOUSLY UNTREATED EAST ASIAN PATIENTS WITH NON-SQUAMOUS CARCINOMA OF THE LUNG HARBORING A TRANSLOCATION OR INVERSION EVENT INVOLVING THE ANAPLASTIC LYMPHOMA KINASE (ALK) GENE LOCUS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: NSCLC (Non-small Cell Lung Cancer)
Keywords: Crizotinib
ALK positive
ALK
Anaplastic Lymphoma Kinase
NSCLC
Non-Small Cell Lung Cancer
Frontline
1L
Previously Untreated
East Asian
Non-Squamous
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-07-12
Enrollment: 207
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase III, Randomized, Open-label, Efficacy and Safety Study of Crizotinib single agent versus Chemotherapy Regimens (Pemetrexed/Cisplatin or Pemetrexed/Carboplatin) in First-Line ALK (Anaplastic Lymphoma Kinase) Positive East Asian Non-Small Cell Lung Cancer Patients. The objective of the study is to demonstrate that Crizotinib is superior to first-line chemotherapy pemetrexed/cisplatin or pemetrexed/carboplatin in prolonging Progression Free Survival (PFS) in East Asian patients with advanced Non-Squamous NSCLC whose tumors harbor a translocation or inversion event involving the ALK (Anaplastic Lymphoma Kinase) gene locus.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically proven diagnosis of locally advanced not suitable for local treatment, recurrent and metastatic non-squamous cell carcinoma of the lung.
* Positive for translocation or inversion events involving the ALK gene locus.
* No prior systemic treatment for locally advanced or metastatic disease. Patients with brain metastases only if treated and neurologically stable for at least 2 weeks and are not taking any medications contraindicated in Exclusion Criteria
* Evidence of a personally signed and dated informed consent document and willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures including completion of patient reported outcome \[PRO\] measures.

Exclusion Criteria:

* Current treatment on another therapeutic clinical trial.
* Prior therapy directly targeting ALK.
* Any of the following within the 3 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack. Appropriate treatment with anticoagulants is permitted.
* Ongoing cardiac dysrhythmias of NCI CTCAE Grade \>=2, uncontrolled atrial fibrillation of any grade, or QTc interval \>470 msec.
* Pregnancy or breastfeeding.
* Use of drugs or foods that are known potent CYP3A inducers/inhibitors Concurrent use of drugs that are CYP3A substrates with narrow therapeutic indices.
* Known HIV infection
* History of extensive disseminated/bilateral or known presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis, but not history of prior radiation pneumonitis.
* Other severe acute or chronic medical conditions (including severe gastrointestinal conditions such as diarrhea or ulcer) or psychiatric conditions, or end-stage renal disease on hemodialysis, or laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration, and which would, therefore, make the patient inappropriate for entry into this study.

Primary outcomes:
measure: Progression-Free Survival (PFS) Based on IRR by Treatment Arm
timeFrame: Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (whichever occurred first, assessed up to 33 months)
Secondary outcomes:
measure: Objective Response Rate (ORR) - Percentage of Participants With Objective Response Based on IRR
timeFrame: Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (assessed up to 33 months)
measure: Overall Survival (OS)
timeFrame: From randomization to death or last date known as alive for those who were lost to follow-up or withdrew consent (assessed up to 64 months).
measure: Percentage of Participants With Disease Control at 12 Weeks Based on IRR
timeFrame: From randomization to Week 12
measure: Estimate of the Percentage of Participants Surviving at 1 Year and at 18 Months
timeFrame: From randomization to 1 year and from randomization to 18 months
measure: Duration of Response (DR) Based on IRR
timeFrame: From objective response to date of progression, death or last tumor assessment without progression before any additional anti-cancer therapy (whichever occurred first, up to 33 months)
measure: Time to Tumor Response (TTR) Based on IRR
timeFrame: Randomization to first documentation of objective tumor response (up to 33 months).
measure: Time to Progression (TTP) Based on IRR
timeFrame: Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (whichever occurred first, up to 33 months)
measure: Intracranial Time to Progression (IC-TTP) Based on IRR
timeFrame: Randomization to objective intracranial progression or last tumor assessment without progression before any additional anti-cancer therapy (whichever occurred first, up to 33 months)
measure: Extracranial Time to Progression (EC-TTP) Based on IRR
timeFrame: Randomization to objective extracranial progression or last tumor assessment without progression before any additional anti-cancer therapy (whichever occurred first, up to 33 months)
measure: Time to Deterioration (TTD) in Participant Reported Pain, Dyspnea, or Cough Assessed Using Quality of Life Questionnaire Supplement Module for Lung Cancer (QLQ-LC13)
timeFrame: From Baseline to deterioration while on study treatment. For participants with no deterioration, the data was censored at the last date when QLQ-LC13 assessment for pain, dyspnea, or cough was completed (assessed up to 33 months）
measure: Change From Baseline in Functioning and Global Quality of Life (QOL) as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
timeFrame: From Baseline to deterioration while on study treatment. For participants with no deterioration, the data was censored at the last date when QLQ-LC13 assessment for pain, dyspnea, or cough was completed (assessed up to 33 months）
measure: Change From Baseline Scores in QLQ-C30 Symptoms as Assessed by the EORTC-QLQ-C30
timeFrame: From Baseline to deterioration while on study treatment. For participants with no deterioration, the data was censored at the last date when QLQ-LC13 assessment for pain, dyspnea, or cough was completed (assessed up to 33 months）
measure: Change From Baseline in Lung Cancer Symptom Scores as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13)
timeFrame: From Baseline to deterioration while on study treatment. For participants with no deterioration, the data was censored at the last date when QLQ-LC13 assessment for pain, dyspnea, or cough was completed (assessed up to 33 months）
measure: Change From Baseline in General Health Status as Assessed by EuroQol 5D (EQ-5D)-Visual Analog Scale (VAS)
timeFrame: From Baseline to deterioration while on study treatment. For participants with no deterioration, the data was censored at the last date when QLQ-LC13 assessment for pain, dyspnea, or cough was completed (assessed up to 33 months）
measure: Change From Baseline in General Health Status as Assessed by EQ-5D-Index
timeFrame: From Baseline to deterioration while on study treatment. For participants with no deterioration, the data was censored at the last date when QLQ-LC13 assessment for pain, dyspnea, or cough was completed (assessed up to 33 months)
measure: Percentage of Participants With Visual Disturbance as Assessed by Visual Symptom Assessment Questionnaire (VSAQ-ALK)
timeFrame: Cycle 1 Day 1 to end of treatment or withdrawal, no later than 4 weeks (+/- 1 week) from last dose of study medication or when the decision was taken to withdraw from the study (whichever was sooner, assessed up to Cycle 86)
measure: Agreement Between Central Laboratory ALK FISH and ALK IHC Test Results - Molecular Profiling Evaluable
timeFrame: During the screening (less than or equal to 28 days prior to dosing)
measure: Percentage of Participants With Treatment-Emergent Adverse Events (AEs; All Causalities)
timeFrame: From the first dose of study medication up to 28 days after the last dose of study medication or up to the time that a participant died or received subsequent anticancer treatment (maximum duration between first and last dose: 324.4 weeks)
measure: Percentage of Participants With Treatment-Emergent AEs (Treatment Related)
timeFrame: From the first dose of study medication up to 28 days after the last dose of study medication or up to the time that a participant died or received subsequent anticancer treatment (maximum duration between first and last dose: 324.4 weeks)
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University, Department of Medical Oncology
state: Anhui
city: Beijing
country: China
facility: Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Dept. of Respiration. Peking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Chest Hospital, Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: Oncology Department, the Second Affiliated Hospital of Third Military Medical University,PLA
state: Chongqing
city: Chongqing
country: China
facility: Oncology Department, XinQiao Hospital of Third Military Medical University,
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Province Oncology Hospital
state: Fujian
city: Guangzhou
country: China
facility: SUN Yat-Sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong General Hospital, Oncology Center
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical College/Thoracic Surgery
state: Guangdong
city: Nanning
country: China
facility: Department 2 of Chemotherapy, Tumour Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology/Cancer Center
state: Hubei
city: Changsha
country: China
facility: Hunan Provincial Tumor Hospital/Division of Oncology
state: Hunan
city: Nanjing
country: China
facility: Nanjing General Hospital of Nanjing Military Command, Department of Respiratory medicine
state: Jiangsu
city: Changchun
country: China
facility: Department of Oncology, Jilin Provincial Cancer Hospital
state: Jilin
city: Shenyang
country: China
facility: The first hospital of China Medical University/Oncology Department
state: Liaoning
city: Chengdu
country: China
facility: Oncology Department, West China Hospital of Sichuan University
state: Sichuan
city: Chengdu
country: China
facility: Sichuan Province Cancer Hospital/Department of Pulmonary Tumor
state: Sichuan
city: Hangzhou
country: China
facility: Department of Respiratory, The First Affiliated Hospital of College of Medicine, Zhejiang University
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital of College of Medicine of Zhejiang University, Center for Oncology
state: Zhejiang
city: Beijing
country: China
facility: 307 Hospital of PLA/Department of Lung Cancer
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: The Military General Hospital of Beijing PLA
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: Chinese PLA General Hospital
city: Beijing
country: China
facility: Beijing Chest Hospital, Capital Medical University
city: Chongqing
country: China
facility: Respiration department,the First Affiliated Hospital of Third Military Medical University, PLA
city: Shanghai
country: China
facility: Shanghai Chest Hospital/Lung cancer clinical center
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University / Respiratory Department
city: Shanghai
country: China
facility: Shanghai First People's Hospital
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
city: Chai Wan
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
city: Kubang Kerian, Kota Bahru
country: Malaysia
facility: Department of Nuclear Medicine, Radiotherapy and Oncology, Hospital Universiti Sains Malaysia
state: Kelantan
city: Georgetown
country: Malaysia
facility: Hospital Pulau Pinang
state: Pulau Pinang
city: Liou Ying Township
country: Taiwan
facility: Chi Mei Medical Center Liouying
state: Tainan
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Tainan city
country: Taiwan
facility: Chi Mei Medical Center Liuying
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital, Chest Department
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation, LinKou Branch
city: Pathumwan
country: Thailand
facility: Medical Oncology Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University
state: Bangkok
city: Bangkok
country: Thailand
facility: Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Siriraj Hospital,
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Wu YL, Lu S, Lu Y, Zhou J, Shi YK, Sriuranpong V, Ho JCM, Ong CK, Tsai CM, Chung CH, Wilner KD, Tang Y, Masters ET, Selaru P, Mok TS. Results of PROFILE 1029, a Phase III Comparison of First-Line Crizotinib versus Chemotherapy in East Asian Patients with ALK-Positive Advanced Non-Small Cell Lung Cancer. J Thorac Oncol. 2018 Oct;13(10):1539-1548. doi: 10.1016/j.jtho.2018.06.012. Epub 2018 Aug 14.