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A Study Of Lorlatinib Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC

This study is currently recruiting participants.
Verified October 2017 by Pfizer
Sponsor:
ClinicalTrials.gov Identifier:
NCT03052608
First Posted: February 14, 2017
Last Update Posted: October 31, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Pfizer
January 20, 2017
February 14, 2017
October 31, 2017
April 14, 2017
February 17, 2020   (Final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT03052608 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
A Study Of Lorlatinib Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC
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
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
Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Carcinoma, Non-Small-Cell Lung
  • Drug: Lorlatinib
    ALK-positive NSCL treatment
    Other Name: PF-06463922
  • Drug: Crizotinib
    ALK-positive NSCL treatment
    Other Name: Xalkori
  • 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
Gainor JF, Shaw AT. J-ALEX: alectinib versus crizotinib in ALK-positive lung cancer. Lancet. 2017 Jul 1;390(10089):3-4. doi: 10.1016/S0140-6736(17)31074-7. Epub 2017 May 10.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
280
October 23, 2023
February 17, 2020   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
Australia,   Belgium,   Canada,   Denmark,   France,   Germany,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Poland,   Russian Federation,   Singapore,   Spain,   Taiwan,   United Kingdom,   United States
 
 
NCT03052608
B7461006
2016-003315-35 ( EudraCT Number )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Yes
Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests
URL: http://
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
October 2017

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