A Study Of Lorlatinib Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Lorlatinib; Crizotinib
Intervention description: ALK-positive NSCL treatment; ALK-positive NSCL treatment
Intervention MeSH terms: Crizotinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 296.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ALK; anaplastic lymphoma kinase; Non-Small-Cell Lung cancer; NSCLC

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
    

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.