Advanced ALK positive non small cell lung cancer MedDRA version: 21.1 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classificatio
Conditions
Sponsors
Pfizer Inc,
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Diagnosis: a.Study Population: Patients with histologically or cytologically confirmed diagnosis of locally advanced [(Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) by American Joint Committee on Cancer (AJCC) v 7.0] ALK-positive NSCLC where ALK status is determined by the FDA-approved (for use in US), CE (Conformité Européene) marked (for EU and other countries that accept CE marking), and PMDA(Pharmaceuticals and Medical Devices Agency)-approved (for use in Japan) Ventana ALK (D5F3) Companion Diagnostic (CDx) IHC test performed on the Ventana ULTRA or XT platforms (refer to Section 6.1.1.1 for any prescreening activity related to ALK determination); b.Tumor Requirements: At least 1 extracranial measurable target lesion per RECIST v. 1.1 that has not been previously irradiated. CNS metastases are allowed if: i.Asymptomatic: either not currently requiring corticosteroid treatment, or on a stable or decreasing dose of = 10 mg QD prednisone or equivalent; or ii.Previously diagnosed and treatment has been completed with full recovery from the acute effects of radiation therapy or surgery prior to randomization, and if corticosteroid treatment for these metastases has been withdrawn for at least 4 weeks with neurological stability; or iii.Leptomeningeal disease (LMD) or carcinomatous meningitis (CM) if visualized on MRI (magnetic resonance imaging), or if baseline CSF positive cytology is available. c.Tissue Requirements: All participants must have an archival formalin fixed, paraffin embedded (FFPE) tissue specimen available and collected prior to randomization. If archived tissue is unavailable, then a mandatory de novo biopsy must be performed. 2.No prior systemic NSCLC treatment, including molecularly targeted agents, angiogenesis inhibitors, immunotherapy, or chemotherapy. Adjuvant/neoadjuvant NSCLC treatment only allowed if completed more than 12 months prior to randomization. 3.Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, 1, or 2. 4.Age =18 years (or =20 years as required by local regulation). 5.Adequate Bone Marrow Function, including: a.Absolute Neutrophil Count (ANC) = 1,500/mm3 or = 1.5 x 109/L; b.Platelets =100,000/mm3 or =100 x 109/L; c.Hemoglobin = 9 g/dL. 6.Adequate Pancreatic Function, including: a.Serum total amylase = 1.5 x upper limit of normal (ULN)*; b.Serum lipase = 1.5 x ULN. *if total amylase > 1.5 x ULN, but pancreatic amylase is within the ULN, then patient may be enrolled. 7.Adequate Renal Function, including: a.Serum creatinine = 1.5 x ULN or estimated creatinine clearance = 60 mL/min as calculated using the method standard for the institution. 8.Adequate Liver Function, including: a.Total serum bilirubin = 1.5 x ULN; b.Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) = 2.5 x ULN (= 5.0 x ULN in case of liver metastases); 9.Acute effects of prior radiotherapy resolved to baseline severity or to CTCAE Grade =1 except for AEs that in the investigator’s judgment do not constitute a safety risk for the participant. 10.Serum pregnancy test (for females of childbearing potential) negative at screening. Female participants of non-childbearing potential must meet at least 1 of the following criteria: •Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle-stimulating
Exclusion criteria
Exclusion criteria: 1.Spinal cord compression unless the participant has good pain control attained through therapy, and there is stabilization or recovery of neurological function for the 4 weeks prior to randomization. 2.Major surgery within 4 weeks prior to randomization. Minor surgical procedures (eg, port insertion) are not excluded, but sufficient time should have passed for adequate wound healing. 3.Radiation therapy within 2 weeks prior to randomization, including stereotactic or partial brain irradiation. Patients who complete whole brain irradiation within 4 weeks prior to randomization or palliative radiation therapy outside of the CNS within 48 hours prior to randomization will also not be included in the study. 4.Gastrointestinal abnormalities, including inability to take oral medication; requirement for intravenous alimentation; prior surgical procedures affecting absorption including total gastric resection or lap band; active inflammatory gastrointestinal disease, chronic diarrhea, symptomatic diverticular disease; treatment for active peptic ulcer disease in the past 6 months; malabsorption syndromes. 5.Known prior or suspected severe hypersensitivity to study drugs or any component in their formulations. 6.Active and clinically significant bacterial, fungal, or viral infection including hepatitis B virus (HBV) or hepatitis C virus (HCV) (e.g., in case of known HBsAg or HCV antibody positivity), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness. 7. Clinically significant vascular (both arterial and venous) and non-vascular cardiac conditions, (active or within 3 months prior to enrollment), which may include, but are not limited to: - Arterial disease such as cerebral vascular accident/stroke (including Transient Ischemic Attack -TIA), myocardial infarction, unstable angina; - Venous diseases such as cerebral venous thrombosis, symptomatic pulmonary embolism; -Non-vascular cardiac disease such as congestive heart failure (New York Heart Association Classification Class = II), second-degree or third-degree AV block (unless paced) or any AV block with PR >220 msec; or ongoing cardiac dysrhythmias of NCI CTCAE Grade =2, uncontrolled atrial fibrillation of any grade, bradycardia defined as 470 msec, or congenital long QT syndrome. 8.Patients with predisposing characteristics for acute pancreatitis according to investigator judgment (eg, uncontrolled hyperglycemia, current gallstone disease) in the last month prior to randomization. 9.History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis. 10.Evidence of active malignancy (other than NSCLC, non melanoma skin cancer, in situ cervical cancer, papillary thyroid cancer, lobular carcinoma in situ/ductal carcinoma in situ (LCIS/DCIS) of the breast, or localized prostate cancer) within the last 3 years prior to randomization. 11.Concurrent use of any of the following food or drugs (consult the sponsor if in doubt whether a food or a drug falls into any of the above categories) within 12 days prior to the first dose of lorlatinib or crizotinib. a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To demonstrate that lorlatinib as a single agent (Arm A) is superior to crizotinib alone (Arm B) in prolonging progression-free survival (PFS) in advanced ALK-positive NSCLC participants who are treatment naïve.;Secondary Objective: - To compare Arm A with Arm B in treatment-naïve advanced ALK-positive NSCLC participants with respect to overall survival (OS); - To evaluate the antitumor activity in each treatment arm; - To evaluate the safety and tolerability in each treatment arm; - To evaluate participant-reported outcomes (PROs) of health-related quality of life, disease/treatment-related symptoms of lung cancer, and general health status for each treatment arm; - To evaluate candidate biomarkers of sensitivity or resistance to single-agent crizotinib or lorlatinib in pre-treatment tumor tissue; - To evaluate candidate biomarkers of sensitivity or resistance to single-agent crizotinib or lorlatinib in peripheral blood. ;Primary end point(s): •PFS based on blinded independent central review (BICR) assessment (RECIST v.1.1).;Timepoint(s) of evaluation of this end point: Please, refer to the Schedule of assessments in the Protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Efficacy: OS, PFS based on Investigator’s assessment, OR based on BICR and on Investigator’s assessment; intracranial OR (IC-OR), IC-TTP, DR and IC-DR, TTR and ICTTR all by BICR (RECIST v. 1.1) and PFS2; •Safety: AEs (as graded by NCI CTCAE v.4.03); laboratory abnormalities (as graded by NCI CTCAE v.4.03); vital signs (blood pressure, pulse rate) and body weight; electrocardiograms (ECGs); echocardiogram or MUGA scan; ophthalmologic data; •PROs as assessed by EORTC QLC-C30, EORTC QLQ-LC13, EQ-5D-5L; •Tumor tissue biomarkers including, but not limited to, ALK gene rearrangement and/or mutation as measured by next-generation sequencing (NGS) and/or immunohistochemistry (IHC); •Peripheral blood cfDNA (circulating free Deoxyribonucleic acid) biomarkers including, but not limited to, ALK gene rearrangement and/or ALK kinase domain mutations. ;Timepoint(s) of evaluation of this end point: Please refer to the Schedule of Activities of the Protocol | — |
Countries
Argentina, Australia, Belgium, Canada, China, Czechia, Czech Republic, Denmark, France, Germany, Hong Kong, India, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Russian Federation, Singapore, Spain, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trials.gov Call Centre
Pfizer Inc
Outcome results
None listed