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Trial record 1 of 1 for:    NCT03052608
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A Study Of Lorlatinib Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC

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ClinicalTrials.gov Identifier: NCT03052608
Recruitment Status : Recruiting
First Posted : February 14, 2017
Last Update Posted : July 30, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE January 20, 2017
First Posted Date  ICMJE February 14, 2017
Last Update Posted Date July 30, 2019
Actual Study Start Date  ICMJE April 14, 2017
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 9, 2017)
Progression-free survival (PFS) based on blinded independent central review (BICR) assessment [ Time Frame: From time of Study Start up to 33 months ]
PFS is defined as the time from randomization to the date of the first documentation of objective progression of disease or death due to any cause, whichever occurs first.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03052608 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 9, 2017)
  • Overall Survival (OS) [ Time Frame: From time of Study Start up to 125 months ]
    OS is defined as time from date of randomization to date of death due to any cause
  • PFS based on Investigator's assessment [ Time Frame: From time of Study Start up to 33 months ]
    PFS is defined as the time from randomization to the date of the first documentation of objective progression of disease or death due to any cause, whichever occurs first.
  • Objective Response (OR) based on BICR and on Investigator's assessments [ Time Frame: From time of Study Start up to 33 months ]
    OR defined as complete response (CR) or partial response (PR) per RECIST version 1.1 recorded from randomization until disease progression or start of new anti-cancer therapy
  • Intracranial Objective Response (IC-OR) based on BICR assessment [ Time Frame: From time of Study Start up to 33 months ]
    IC-OR defined as complete response (CR) or partial response (PR) based on intracranial disease in the subset of patients with at least 1 intracranial lesion per RECIST version 1.1 (modified) recorded from randomization until disease progression or start of new anti-cancer therapy
  • Intracranial Time to Progression (IC-TTP) based on BIRC assessment [ Time Frame: From time of Study Start up to 33 months ]
    IC-TTP defined as the time from randomization to the date of the first documentation of objective progression of intracranial disease, based on either new brain metastases or progression of existing brain metastases
  • Duration of Response (DR) based on BIRC assessment [ Time Frame: From time of Study Start up to 33 months ]
    DR defined, for patients with an OR per RECIST version 1.1, as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first
  • Time to Tumor Response (TTR) based on BIRC assessment [ Time Frame: From time of Study Start up to 33 months ]
    TTR defined, for patients with a confirmed OR, as the time from the date of randomization to the first documentation of objective response (CR or PR) which is subsequently confirmed
  • Clinical Benefit Response (CBR) based on BIRC assessment [ Time Frame: From time of Study Start up to 33 months ]
    CBR defined as Best Overall Response of confirmed CR or PR at any time, or SD lasting at least 24 weeks from randomization
  • PFS2 based on investigator's assessment [ Time Frame: From time of Study Start up to 45 months ]
    PFS2 is defined as the time from randomization to the date of progression of disease on first subsequent systemic anti-cancer therapy, or death from any cause, whichever occurs first
  • Adverse Event (AE) as graded by NCI CTCAE v 4.03) [ Time Frame: From time of Study Start up to 33 months ]
    Frequency of patients experiencing treatment-emergent AEs (TEAEs)
  • Laboratory abnormalities as graded by NCI CTCAE v 4.03) [ Time Frame: From time of Study Start up to 33 months ]
    Frequency of patients with laboratory test abnormalities
  • Vital signs (blood pressure, pulse rate) and body weight [ Time Frame: From time of Study Start up to 33 months ]
    Summary of actual values and changes from baseline
  • Electrocardiograms (ECG) [ Time Frame: From time of Study Start up to 33 months ]
    Summary of actual values and changes from baseline
  • Echocardiograms or multigated acquisition scan (MUGA) [ Time Frame: From time of Study Start up to 33 months ]
    Summary of actual values and changes from baseline
  • Ophthalmology [ Time Frame: From time of Study Start up to 33 months ]
    Summary of changes from screning results
  • PRO as assessed by EORTC QLQ-C30, EORTC QLQ LC13, and EQ-5D-5L [ Time Frame: From time of Study Start up to 33 months ]
    Summary of absolute scores and mean change of absolute scores from baseline
  • Tumor tissue biomarkers [ Time Frame: From time of Study Start up to 33 months ]
    Summary of baseline levels and changes from baseline
  • Peripheral blood cfDNA (circulating free Deoxyribonucleic acid) biomarkers [ Time Frame: From time of Study Start up to 33 months ]
    Summary of baseline levels and changes from baseline
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Of Lorlatinib Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC
Official Title  ICMJE 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
Brief Summary 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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE
  • Drug: Lorlatinib
    ALK-positive NSCL treatment
    Other Name: PF-06463922
  • Drug: Crizotinib
    ALK-positive NSCL treatment
    Other Name: Xalkori
Study Arms  ICMJE
  • Experimental: Lorlatinib
    Lorlatinib single agent, 100 mg (4 x 25 mg) oral tables, QD, continuously
    Intervention: Drug: Lorlatinib
  • Active Comparator: Crizotinib
    Crizotinib single agent, 250 mg (1 x 250) oral capsules, BID, continuously
    Intervention: Drug: Crizotinib
Publications *

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 9, 2017)
280
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 1, 2024
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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 2.
  • Age ≥18 years .
  • Adequate Bone Marrow, Liver, Renal, Pancreatic Function
  • Negative pregnancy test for females of childbearing potential

Exclusion Criteria:

  • 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.

    1. known strong CYP3A inhibitors .
    2. known strong CYP3A inducers
    3. 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.
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: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Canada,   China,   Czechia,   France,   Germany,   Hong Kong,   India,   Italy,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   Poland,   Russian Federation,   Singapore,   Spain,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries Denmark
 
Administrative Information
NCT Number  ICMJE NCT03052608
Other Study ID Numbers  ICMJE B7461006
2016-003315-35 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date July 2019

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