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Trial record 1 of 1 for:    NCT01945021
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Phase II Safety and Efficacy Study of Crizotinib in East Asian Patients With ROS1 Positive, ALK Negative Advanced NSCLC

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ClinicalTrials.gov Identifier: NCT01945021
Recruitment Status : Completed
First Posted : September 18, 2013
Results First Posted : August 1, 2016
Last Update Posted : May 5, 2020
Sponsor:
Collaborator:
OxOnc Development LP
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE September 5, 2013
First Posted Date  ICMJE September 18, 2013
Results First Submitted Date  ICMJE July 28, 2016
Results First Posted Date  ICMJE August 1, 2016
Last Update Posted Date May 5, 2020
Actual Study Start Date  ICMJE September 30, 2013
Actual Primary Completion Date July 31, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 28, 2016)
Independent Radiology Reviewed Overall Objective Response (ORR) [ Time Frame: Starting from the first dose study treatment until the first documented CR or PR. ]
Overall Objective Response (ORR) was defined as the number of patients with a best overall response of confirmed Complete Response or confirmed Partial Response according to RECIST v1.1 (as determined by Independent Radiology Review [IRR]), relative to the total population of response-evaluable patients (n=127). Confirmed responses were those that persisted on repeat imaging at least 4 weeks after the initial documentation of response.
Original Primary Outcome Measures  ICMJE
 (submitted: September 13, 2013)
Objective Response Rate (ORR) [ Time Frame: From the start of study treatment, until progression until 6 months after the last subject is enrolled on the trial ]
ORR is defined as the percent of patients with a confirmed CR or PR according to RECIST v1.1, relative to the total population of response evaluable patients.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 28, 2016)
  • Duration of Response by Independent Review [ Time Frame: Every 8 or 12 weeks until 6 months after the last patient was enrolled in the trial ]
    The time from the first documentation of objective tumor response (CR or PR) according to Independent Review and that was subsequently confirmed to the first documentation of objective disease progression or to death due to any cause, whichever occurs first. It was calculated for the response evaluable population in the subgroup of patients with a confirmed objective response and who had a subsequent event of progression or death without progression. Patients who did not meet these criteria were censored on the date of the last on-study tumor assessment.
  • Time to First Response [ Time Frame: From date of first dose of crizotinib every 8 weeks or 12 weeks until first documentation of objective response is observed, until 6 months after the last subject is enrolled on the trial ]
    Time to response is defined as the time from the date of first dose to first documentation of objective tumor response (CR or PR), as assessed by Independent Radiology Review, that is subsequently confirmed. For patients proceeding from PR to CR, the onset of PR is taken as the onset of response.
  • Disease Control Rate at 8 Weeks by Independent Radiology Review [ Time Frame: Measured once at 8 weeks after the start of study treatment ]
    The Disease Control Rate at 8 weeks is defined as the number of patients with a confirmed CR, confirmed PR, or SD at 8 weeks, respectively, according to RECIST v1.1 (as determined by IRR), relative to the total population of response evaluable patients.
  • Progression Free Survival Assessed by Independent Radiology Review [ Time Frame: From the date of first dose of crizotinib every 8 weeks or 12 weeks until the first documentation of objective disease progression or death ]
    Progression Free Survival is defined as the time from the date of the first dose of crizotinib to first documentation of objective disease progression or to death on study due to any cause, whichever occurs first. Patients who had neither progression nor death without objective progression were censored at the time of data cut off.
  • Overall Survival [ Time Frame: Assessed from date of date of the first dose of crizotinib until the date of death from any cause, assessed up to 6 months after the last subject is enrolled on the trial ]
  • Type, Incidence, Severity, Seriousness and Relationship to Study Medications of Adverse Events (AE) and Any Laboratory Abnormalities [ Time Frame: From the date of signed informed consent, then a minimum of every 4 weeks until 32 weeks, then a minimum of every 8 weeks, or until 4 weeks after last dose of treatment ]
    Incidence of patients experiencing a treatment emergent adverse events were summarized by type, incidence, severity, seriousness and relationship to study medication.
  • Number of Patients With a Shift in Hematology Laboratory Results From Grade </=2 to Grade 3 or Grade 4 [ Time Frame: From time of baseline screening test every 4, 8, or 12 weeks until 28 days from last dose of study treatment ]
    A summary of the number of patients in the safety population with available laboratory data whose hematology laboratory results shifted from a baseline value of Grade </=2 to a post-baseline result of Grade 3 or Grade 4
  • Number of Patients With a Shift of Chemistry Laboratory Results From Grade </= 2 to Grade 3 or Grade 4 [ Time Frame: From time of baseline screening test every 4, 8, or 12 weeks until 28 days from last dose of study treatment ]
    A summary of the number of patients in the safety population with available laboratory data whose chemistry laboratory results shifted from a baseline value of Grade </=2 to a post-baseline result of Grade 3 or Grade 4
  • Change From Baseline Scores on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) [ Time Frame: From the date of informed consent every 8 weeks or 12 weeks until cycle 8 ]
    The QLQ-C30 consists of 30 questions which are incorporated into 5 functional domains (physical, role, cognitive, emotional, and social domains); a global health status/global QOL scale; 3 symptom scales (fatigue, pain, nausea and vomiting scales); and 6 single items that assess the additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and the perceived financial burden of treatment. Scores for each sub-scale range from 0 to 100. Negative change from baseline scores indicated an improvement in symptoms, decreased functioning, or decreased global QOL, while positive change from baseline scores indicated an improvement in functioning, improvement in global QOL, or a worsening of symptoms. A clinically meaningful change was defined as a >/= 10-point change in mean scores. Changes were described as statistically significant if the 95% CI for the change did not include 0.
  • Change From Baseline Scores on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 [ Time Frame: From the date of informed consent every 8 weeks or 12 weeks until cycle 8 ]
    The QLQ-LC13 consisted of 1 multi-item scale and 9 single items that assessed specific symptoms (dyspnea, cough, hemoptysis, and site-specific pain), side effects (sore mouth, dysphagia, neuropathy, and alopecia), and pain medication use. Negative change from baseline scores indicated an improvement in symptoms, decreased functioning, or decreased global QOL, while positive change from baseline scores indicated an improvement in functioning, improvement in global QOL, or a worsening of symptoms. Scores on each sub-scale range from 0 - 100. A clinically meaningful change was defined as a >/= 10-point change in mean scores. Changes were described as statistically significant if the 95% CI for the change did not include 0.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2013)
  • Type, Incidence, Severity, Seriousness and Relationship to Study Medications of Adverse Events (AE) and Any Laboratory Abnormalities [ Time Frame: From the date of signed informed consent, then a minimum of every 4 weeks until 32 weeks, then a minimum of every 8 weeks, or until 4 weeks after last dose of treatment ]
    Includes all enrolled patients who receive at least one dose of study medication.
  • Disease Control Rate [ Time Frame: Measured once at 8 weeks after the start of study treatment ]
    The percent of patients with a confirmed CR, confirmed PR, or SD at 8 weeks, respectively, according to RECIST 1.1 (as determined by IRR), relative to the total population of response evaluable patients.
  • Progression Free Survival [ Time Frame: Every 8 weeks or 12 weeks until progression until 6 months after last subject is enrolled on the trial ]
    Progression Free Survival is defined as the time from the date of the first dose of crizotinib to first documentation of objective disease progression or to death on study due to any cause, whichever occurs first
  • Time to Response [ Time Frame: Every 8 weeks or 12 weeks until objective response is observed, until 6 months after the last subject is enrolled on the trial ]
    Time to response is defined as the time from the date of first dose to first documentation of objective tumor response (CR or PR) that is subsequently confirmed
  • Patient Reported Outcomes [ Time Frame: From the date of informed consent every 8 weeks or 12 weeks until 6 months after the last subject is enrolled on the trial ]
  • Overall Survival [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 18 months after the last subject is enrolled on the trial ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Safety and Efficacy Study of Crizotinib in East Asian Patients With ROS1 Positive, ALK Negative Advanced NSCLC
Official Title  ICMJE 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
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non Small Cell Lung Cancer
  • ROS1 Proto Oncogene
  • Crizotinib
Intervention  ICMJE Drug: Crizotinib
Other Name: Xalkori
Study Arms  ICMJE Experimental: Crizotinib
Single-arm trial whereby all consented, enrolled, eligible patients receive crizotinib
Intervention: Drug: Crizotinib
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 28, 2016)
129
Original Estimated Enrollment  ICMJE
 (submitted: September 13, 2013)
110
Actual Study Completion Date  ICMJE January 22, 2020
Actual Primary Completion Date July 31, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China,   Japan,   Korea, Republic of,   Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01945021
Other Study ID Numbers  ICMJE OO 12-01
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE OxOnc Development LP
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP