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
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) Assessment — From time of Study Start up to 33 months PFS was defined as the time from randomization to the date of the first documentation of progressive disease as assessed by the independent radiologist or death due to any cause, whichever occurred first. PFS (in months) was calculated as (date of event or censoring-randomization+1)/30.4375. Progressive disease is defined per RECIST version 1.1, as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.
Trial sites (166)
Facility
City
Region
Status
Florida Cancer Specialists
Altamonte Springs
Florida
Florida Cancer Specialists
Brandon
Florida
Florida Cancer Specialists
Clearwater
Florida
Florida Cancer Specialists
Gainesville
Florida
Florida Cancer Specialists
Largo
Florida
Florida Cancer Specialists
Lecanto
Florida
Florida Cancer Specialists
Orange City
Florida
Florida Cancer Specialists
Orlando
Florida
Florida Cancer Specialists
Spring Hill
Florida
Florida Cancer Specialists
St. Petersburg
Florida
Florida Cancer Specialists
Tampa
Florida
Florida Cancer Specialists
Tavares
Florida
Florida Cancer Specialists
The Villages
Florida
Florida Cancer Specialists
Winter Park
Florida
Massachusetts Eye and Ear Infirmary
Boston
Massachusetts
Massachusetts General Hospital
Boston
Massachusetts
Ophthalmic Consultants of Boston Inc
Boston
Massachusetts
The William P. Beetham Eye Institute, Joslin Diabetes Center
Boston
Massachusetts
University of Rochester Cancer Center Pharmacy
Rochester
New York
University of Rochester Medical Center
Rochester
New York
Tennessee Oncology, PLLC
Dickson
Tennessee
Tennessee Oncology, PLLC
Franklin
Tennessee
Tennessee Oncology, PLLC
Gallatin
Tennessee
Tennessee Oncology, PLLC
Hermitage
Tennessee
Tennessee Oncology, PLLC
Lebanon
Tennessee
Tennessee Oncology, PLLC
Murfreesboro
Tennessee
Tennessee Oncology, PLLC
Nashville
Tennessee
The Sarah Cannon Research Institute.
Nashville
Tennessee
Tennessee Oncology, PLLC
Nashville
Tennessee
Tennessee Oncology, PLLC
Nashville
Tennessee
Tennessee Oncology, PLLC
Nashville
Tennessee
Tennessee Oncology, PLLC
Shelbyville
Tennessee
Tennessee Oncology, PLLC
Smyrna
Tennessee
University of Washington Medical Center
Seattle
Washington
Centro de Investigacion Pergamino SA
Pergamino
Buenos Aires
Centro Medico Austral
CABA
Argentina
Bendigo Day Surgery Collection Centre and Laboratory
Bendigo
Victoria
Bendigo Medical Imaging, Bendigo Hospital
Bendigo
Victoria
Melbourne Pathology
Bendigo
Victoria
Peter MacCallum Cancer Centre
Melbourne
Victoria
+ 126 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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