Clinical trial NCT01945021: Phase II Safety and Efficacy Study of Crizotinib in East Asian Patients With ROS1 Positive, ALK Negative Advanced NSCLC
Official title: Phase II, Open Label, Single Arm Study of the Efficacy and Safety of Crizotinib in East Asian Patients With Advanced ALK-Negative NSCLC Harboring a Translocation or Inversion Involving the c-ROS Oncogene (ROS1) Locus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
ROS1 Proto Oncogene
Crizotinib
Keywords: Non small cell lung cancer
NSCLC
ROS1
ROS1 positive
ROS1 proto oncogene
c ros tyrosine kinases
ROS1 positive NSCLC
ROS1 lung cancer
ALK negative
Lung Carcinoma
Neoplasm
Crizotinib
Xalkori
Previously treated or untreated
North East Asian
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: OxOnc Development LP
First posted: 2013-09-18
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To assess treatment effectiveness and safety of oral crizotinib administered to East Asian patients with Advanced Non-Small Cell Lung Cancer (NSCLC) that is confirmed to be positive for a ROS1 positive gene mutation (translocation or inversion) and confirmed negative for an ALK mutation


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically proven diagnosis of NSCLC that is locally advanced or metastatic
* treatment-naïve or have received no more than 3 systemic treatment regimen(s)
* Positive for translocation or inversion events involving the ROS1 gene
* Negative for translocation or inversion events involving the ALK gene
* Patients with brain metastases are eligible if asymptomatic, or if treated, must be neurologically stable for at least 2 weeks and are not taking any contraindicated medications
* Any prior treatment (chemotherapy, radiation \[except for palliative\], or surgery) must have been completed at least 2 weeks prior to initiation of study medication
* At least 1 measurable tumor lesion as per RECIST v1.1
* Female or male, 18 years of age or older
* ECOG performance status 0 to 1
* Adequate organ function
* Signed and dated informed consent
* Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including completion of the PRO measures
* Agree to use effective contraception during the study period and for at least 90 days after completion of the study treatment

Exclusion Criteria:

* Current treatment on another therapeutic clinical trial
* Prior therapy specifically directed against ALK or ROS1 fusion genes
* Spinal cord compression unless treated with the patient attaining good pain control and stable or recovered neurologic function, carcinomatous meningitis, or leptomeningeal disease
* known interstitial fibrosis or interstitial lung disease
* myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack within 3 months prior to start of study treatment
* Ongoing cardiac dysrhythmias of NCI CTCAE v4.03 Grade \>/=2, uncontrolled atrial fibrillation of any grade, or QTc \>470 msec
* Pregnant or breast feeding
* Use of drugs or foods that are known potent CYP3A4 inhibitors or inducers
* Use of other anti-cancer drugs including traditional Chinese medicine on the SFDA list
* Evidence of active malignancy within last 3 years

Primary outcomes:
measure: Independent Radiology Reviewed Overall Objective Response (ORR)
timeFrame: Starting from the first dose study treatment until the first documented CR or PR (every 8 weeks then after 8 cycles at every 12 weeks in duration of 94.0 weeks)
Secondary outcomes:
measure: IRR-Assessed Duration of Response (DR)
timeFrame: From first documentation of objective tumor response to first documentation of objective PD or death due to any cause, whichever occurred first (every 8 weeks then after 8 cycles at every 12 weeks in duration of 151.3 weeks)
measure: IRR-Assessed Time to Tumor Response (TTR)
timeFrame: From date of first dose of crizotinib to first documentation of objective response was observed (every 8 weeks then after 8 cycles at every 12 weeks in duration of 151.3 weeks)
measure: IRR Assessed Disease Control Rate (DCR) at 8 Weeks
timeFrame: At 8 weeks after the start of study treatment
measure: IRR-Assessed Progression Free Survival (PFS)
timeFrame: From the date of first dose of crizotinib until the first documentation of objective PD or death (every 8 weeks then after 8 cycles at every 12 weeks in duration of 151.3 weeks)
measure: Overall Survival (OS)
timeFrame: From date of the first dose of crizotinib until the date of death from any cause (up to 291.9 weeks)
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs, Treatment Emergent Treatment Related AEs and SAEs, Grade 3 or 4 Treatment Emergent AEs and Grade 3 or 4 Treatment Emergent Treatment Related AEs
timeFrame: Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks)
measure: Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4
timeFrame: Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks)
measure: Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4
timeFrame: Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks)
measure: Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores
timeFrame: Baseline up to Cycle 60
measure: Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 Scores
timeFrame: Baseline up to Cycle 60
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University, Department of Medical Oncology
state: Anhui
city: Chaoyang District
country: China
facility: Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Dongcheng District
country: China
facility: The Military General Hospital of Beijing PLA / Medical Oncology Dept.
state: Beijing
city: Fengtai District
country: China
facility: 307 Hospital of PLA/Department of Lung Cancer
state: Beijing
city: Haidian District
country: China
facility: Beijing Cancer Hospital, Department of Thoracic Oncology
state: Beijing
city: Haidian District
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Tongzhou District
country: China
facility: Beijing Chest Hospital
state: Beijing
city: Shapingba District
country: China
facility: Respiration department,the First Affiliated Hospital of Third Military Medical University, PLA
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: The First Affiliated Hospital of Guangzhou Medical College
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Changsha
country: China
facility: Hunan Provincial Tumor Hospital/Division of Oncology
state: Hunan
city: Changchun
country: China
facility: Department of Oncology, Jilin Provincial Cancer Hospital
state: Jilin
city: Qingdao
country: China
facility: The affiliated hospital of medical college Qingdao University / Medical oncology department
state: Shandong
city: Shanghai
country: China
facility: Department of Pulmonary Medicine, Shanghai Chest Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Chest Hospital/Lung cancer clinical center
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
city: Xuhui District
country: China
facility: Zhongshan Hospital Fudan University / Respiratory Department
state: Shanghai
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: Hexi District
country: China
facility: Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: 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: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Aichi
country: Japan
facility: Aichi Cancer Center Hospital
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Ehime
country: Japan
facility: NHO Shikoku Cancer Center
city: Fukuoka
country: Japan
facility: NHO Kyushu Cancer Center
city: Hyogo
country: Japan
facility: Hyogo Cancer Center
city: Miyagi
country: Japan
facility: Tohoku University Hospital
city: Osaka
country: Japan
facility: Kinki University Hospital
city: Osaka
country: Japan
facility: Osaka City General Hospital
city: Tokyo
country: Japan
facility: Cancer Institute Hospital of JFCR
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University, Severance Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Wu YL, Yang JC, Kim DW, Lu S, Zhou J, Seto T, Yang JJ, Yamamoto N, Ahn MJ, Takahashi T, Yamanaka T, Kemner A, Roychowdhury D, Paolini J, Usari T, Wilner KD, Goto K. Phase II Study of Crizotinib in East Asian Patients With ROS1-Positive Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2018 May 10;36(14):1405-1411. doi: 10.1200/JCO.2017.75.5587. Epub 2018 Mar 29.