Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC)
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive as assessed by the Ventana IHC test. Sufficient tumor tissue to perform ALK IHC and ALK FISH is required. Both tests will be performed at designated central laboratories. •Measurable disease (by RECIST v1.1) prior to the administration of study treatment. •Patients had no prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC. •ECOG PS of 0 2. •Adequate hematologic, renal and liver function. •Patients must have recovered from effects of any major surgery or significant traumatic injury at least 28 days before the first dose of study treatment. •Prior brain or leptomeningeal metastases allowed if asymptomatic (e.g., diagnosed incidentally at study baseline). Asymptomatic CNS lesions might be treated at the discretion of the investigator as per local clinical practice. If patients have neurological symptoms or signs due to CNS metastasis, patients need to complete whole brain radiation or gamma knife irradiation treatment. In all cases, radiation treatment must be completed at least 14 days before enrollment and patients must be clinically stable. •Able and willing to provide written informed consent prior to performing any study related procedures and to comply with the study protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 233 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: •Patients with a previous malignancy within the past 3 years are excluded (other than curatively treated basal cell carcinoma of the skin,early gastrointestinal (GI) cancer by endoscopic resection, in situ carcinoma of the cervix, or any cured cancer that is considered to have no impact in PFS and OS for the current NSCLC). •Any gastrointestinal (GI) disorder that may affect absorption of oral medications, such as mal-absorption syndrome or status post-major bowel resection. •National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) Grade 3 or higher toxicities due to any prior therapy such as radiotherapy (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication •Co-administration of anti-cancer therapies other than those administered in this study •Liver disease characterized by: ALT or AST > 3 × upper limit of normal (ULN; = 5 × ULN for patients with concurrent liver metastasis) confirmed on two consecutive measurements OR Impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices OR Acute viral or active autoimmune, alcoholic, or other types of acute hepatitis •Patients with baseline QTc > 470 milliseconds (ms) or symptomatic bradycardia •Administration of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the first dose of study treatment and while on treatment with alectinib or crizotinib •Administration of agents with potential QT interval prolonging effects within 14 days prior to the first administration of study drugfor all patients and while on treatment through the end of the study for crizotinib-treated patients only. •History of organ transplant •Pregnant or lactating women •Known HIV positivity or AIDS-related illness •History of hypersensitivity to any of the additives in the alectinib drug formulation •History of hypersensitivity to any of the additives in the crizotinib drug formulation •Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications or that would, in the opinion of the Principal Investigator, pose an unacceptable risk to the patient in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Investigator assessed progression-free survival (PFS);Secondary Objective: PFS by the independent review committee (IRC); time to CNS progression by IRC; Objective Response Rate (ORR) and Duration of Response (DOR); time to deterioration (TTD) in patient-reported lung cancer symptoms; health-related quality of life (HRQoL); safety and tolerability; pharmacokinetics of alectinib and metabolite(s); overall survival (OS).;Primary end point(s): PFS, as assessed by investigator;Timepoint(s) of evaluation of this end point: The time from date of randomization to the date of first documented disease progression (as per RECIST 1.1) or death, whichever occurs first | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 PFS by IRC 2 Time to CNS Progression by IRC 3 ORR 4 DOR 5 Time to deterioration (TTD) in patient-reported lung cancer symptoms 6 Health-related quality of life (HRQoL) 7 Safety and tolerability 8 Pharmacokinetics of alectinib and metabolite(s) 9 Overall survival (OS);Timepoint(s) of evaluation of this end point: 1 The same methodology as specified for PFS 2 The time from randomization until radiographic evidence of CNS progression 3 The percentage of patients who attain a CR or PR (as per RECIST 1.1) 4. The time from when response (CR or PR) was first documented to first documented disease progression or death (whichever occurs first) 5-6 From baseline until disease progression and during post-progression on treatment in case of isolated, asymptomatic CNS progression; at the post-treatment visit (4 weeks after permanent treatment discontinuation); and at survival follow-up for 6 months 7 Throughout the study 8 Until disease progression 9 The time from the date of randomization to the date of death due to any cause | — |
Countries
Australia, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Chile, China, Costa Rica, Czechia, Denmark, Dominican Republic, Egypt, France, Germany, Greece, Guatemala, Hong Kong, Hungary, Israel, Italy, Korea, Republic of, Mexico, New Zealand, Peru, Poland, Portugal, Romania, Russian Federation, Serbia, Singapore, Spain, Switzerland, Taiwan, Thailand, Türkiye, Ukraine, United Kingdom
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed