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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 : September 13, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

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

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: Lorlatinib Drug: Crizotinib Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 280 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 14, 2017
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : February 1, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Crizotinib

Arm Intervention/treatment
Experimental: Lorlatinib
Lorlatinib single agent, 100 mg (4 x 25 mg) oral tables, QD, continuously
Drug: Lorlatinib
ALK-positive NSCL treatment
Other Name: PF-06463922

Active Comparator: Crizotinib
Crizotinib single agent, 250 mg (1 x 250) oral capsules, BID, continuously
Drug: Crizotinib
ALK-positive NSCL treatment
Other Name: Xalkori




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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)

  11. 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

  12. 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

  13. Electrocardiograms (ECG) [ Time Frame: From time of Study Start up to 33 months ]
    Summary of actual values and changes from baseline

  14. 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

  15. Ophthalmology [ Time Frame: From time of Study Start up to 33 months ]
    Summary of changes from screning results

  16. 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

  17. Tumor tissue biomarkers [ Time Frame: From time of Study Start up to 33 months ]
    Summary of baseline levels and changes from baseline

  18. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03052608


Contacts
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Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

  Show 192 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03052608     History of Changes
Other Study ID Numbers: B7461006
2016-003315-35 ( EudraCT Number )
First Posted: February 14, 2017    Key Record Dates
Last Update Posted: September 13, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
ALK; anaplastic lymphoma kinase; Non-Small-Cell Lung cancer; NSCLC
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Crizotinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action