Anaplastic lymphoma kinase-positive (ALK-positive) non-small cell lung cancer (NSCLC) MedDRA version: 20.0 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: 20.0 Level: PT Classification code 10029521 Term:
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. ALK positivity must have been determined by a validated FISH test (recommended probe, Vysis ALK Break-Apart Probe) or a validated immunohistochemistry (IHC) test (recommended antibody, clone D5F3). - Patient had received two prior systemic lines of therapy for advanced or metastatic disease, which must have included one line of platinum-based chemotherapy and one line of crizotinib (progression on or intolerability to crizotinib) - Prior CNS or leptomeningeal metastases allowed if asymptomatic. - Patients with symptomatic CNS metastases for whom radiotherapy is not an option will be allowed to participate in this study - Measurable disease (by Response Evaluation Criteria in Solid Tumors v1.1) prior to the administration of study treatment - Age >=18 years old - Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–2 - Adequate hematologic and renal function - Life expectancy of at least 12 weeks - For all females of childbearing potential, a negative pregnancy test must be obtained prior to randomization within 3 days before starting study treatment - For women who are not postmenopausal (>=12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of =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 or in situ carcinoma of the cervix) -Patients who have received any previous ALK inhibitor other than crizotinib -Any GI disorder that may affect absorption of oral medications, such as mal-absorption syndrome or status post-major bowel resection -Patients with liver disease -National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 Grade 3 or higher toxicities due to any prior therapy (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication -History of organ transplant -Patients with baseline QTc >470 milliseconds or symptomatic bradycardia -Pregnant or lactating women -Known HIV positivity or AIDS-related illness -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: To evaluate and compare between treatment groups the efficacy of alectinib versus chemotherapy in patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) who were previously treated with chemotherapy and crizotinib (progressed or intolerant to crizotinib), as measured by investigator-assessed progression-free survival (PFS); Secondary Objective: •To evaluate and compare between treatment groups central nervous system (CNS) objective response rate (C-ORR) in patients with measurable CNS metastases at Baseline (by IRC) •To evaluate and compare between treatment arms PFS (by IRC);objective response rate (ORR); disease control rate (DCR) and duration of response (DOR) in all patients (by investigator and IRC);time to CNS progression, CNS duration of response (C-DOR), CNS disease control rate (C-DCR) and C-ORR for all patients with baseline CNS metastasis (by IRC), and overall survival (OS) •To evaluate safety and tolerability of alectinib compared with chemotherapy in all patients and patients with CNS metastases at Baseline •To characterize pharmacokinetics of alectinib and its major metabolite(s) •To evaluate and compare time to deterioration in patient-reported lung cancer symptoms •To evaluate and compare patient-reported outcomes of health-related quality of life patient functioning and side effects of treatment ;Primary end point(s): PFS as measured by investigator;Timepoint(s) of evaluation of this end point: Up to 14 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. PFS by Independent Review Committee (IRC) 2. ORR (by investigator and IRC) and C-ORR (IRC) 3. DCR (by investigator and IRC) and C-DCR (IRC) 4. DOR (by investigator and IRC) and C-DOR (IRC) 5. OS 6. Time to CNS progression (IRC) 7. Incidence of adverse events and serious adverse events 8. Safety laboratory tests, Vital signs and ECG 9. Pharmacokinetics of alectinib and metabolite(s) 10. EORTC QLQ-C30 and EORTC QLQ-LC13 scores and the EuroQoL 5 Dimension (EQ-5D-5L) questionnaire score ; Timepoint(s) of evaluation of this end point: 1-8. Upto 14 months 9. Pre-dose at Baseline, Week 3 and Week 6 10. Upto 14 months | — |
Countries
Belgium, Bulgaria, France, Germany, Hong Kong, Hungary, Italy, Korea, Republic of, Norway, Poland, Portugal, Russian Federation, Slovakia, Spain, Turkey
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd
Outcome results
None listed