Clinical Trials /

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

NCT03052608

Description:

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

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: B7461006
  • SECONDARY ID: 2016-003315-35
  • NCT ID: NCT03052608

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
LorlatinibPF-06463922Lorlatinib
CrizotinibXalkoriCrizotinib

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
LorlatinibExperimentalLorlatinib single agent, 100 mg (4 x 25 mg) oral tables, QD, continuously
  • Lorlatinib
CrizotinibActive ComparatorCrizotinib single agent, 250 mg (1 x 250) oral capsules, BID, continuously
  • Crizotinib

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS) based on blinded independent central review (BICR) assessment
Time Frame:From time of Study Start up to 33 months
Safety Issue:
Description: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

Measure:Overall Survival (OS)
Time Frame:From time of Study Start up to 125 months
Safety Issue:
Description:OS is defined as time from date of randomization to date of death due to any cause
Measure:PFS based on Investigator's assessment
Time Frame:From time of Study Start up to 33 months
Safety Issue:
Description: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.
Measure:Objective Response (OR) based on BICR and on Investigator's assessments
Time Frame:From time of Study Start up to 33 months
Safety Issue:
Description: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
Measure:Intracranial Objective Response (IC-OR) based on BICR assessment
Time Frame:From time of Study Start up to 33 months
Safety Issue:
Description: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
Measure:Intracranial Time to Progression (IC-TTP) based on BIRC assessment
Time Frame:From time of Study Start up to 33 months
Safety Issue:
Description: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
Measure:Duration of Response (DR) based on BIRC assessment
Time Frame:From time of Study Start up to 33 months
Safety Issue:
Description: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
Measure:Time to Tumor Response (TTR) based on BIRC assessment
Time Frame:From time of Study Start up to 33 months
Safety Issue:
Description: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
Measure:Clinical Benefit Response (CBR) based on BIRC assessment
Time Frame:From time of Study Start up to 33 months
Safety Issue:
Description:CBR defined as Best Overall Response of confirmed CR or PR at any time, or SD lasting at least 24 weeks from randomization
Measure:PFS2 based on investigator's assessment
Time Frame:From time of Study Start up to 45 months
Safety Issue:
Description: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
Measure:Adverse Event (AE) as graded by NCI CTCAE v 4.03)
Time Frame:From time of Study Start up to 33 months
Safety Issue:
Description:Frequency of patients experiencing treatment-emergent AEs (TEAEs)
Measure:Laboratory abnormalities as graded by NCI CTCAE v 4.03)
Time Frame:From time of Study Start up to 33 months
Safety Issue:
Description:Frequency of patients with laboratory test abnormalities
Measure:Vital signs (blood pressure, pulse rate) and body weight
Time Frame:From time of Study Start up to 33 months
Safety Issue:
Description:Summary of actual values and changes from baseline
Measure:Electrocardiograms (ECG)
Time Frame:From time of Study Start up to 33 months
Safety Issue:
Description:Summary of actual values and changes from baseline
Measure:Echocardiograms or multigated acquisition scan (MUGA)
Time Frame:From time of Study Start up to 33 months
Safety Issue:
Description:Summary of actual values and changes from baseline
Measure:Ophthalmology
Time Frame:From time of Study Start up to 33 months
Safety Issue:
Description:Summary of changes from screning results
Measure: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
Safety Issue:
Description:Summary of absolute scores and mean change of absolute scores from baseline
Measure:Tumor tissue biomarkers
Time Frame:From time of Study Start up to 33 months
Safety Issue:
Description:Summary of baseline levels and changes from baseline
Measure:Peripheral blood cfDNA (circulating free Deoxyribonucleic acid) biomarkers
Time Frame:From time of Study Start up to 33 months
Safety Issue:
Description:Summary of baseline levels and changes from baseline

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pfizer

Trial Keywords

  • ALK; anaplastic lymphoma kinase; Non-Small-Cell Lung cancer; NSCLC

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