ALK-rearranged non-small cell lung cancer (NSCLC) after disease progression on prior ALK inhibitor therapy 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
Conditions
Sponsors
ROCHE SAS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients with histologically or cytologically confirmed locally advanced or metastatic NSCLC (Stage IIIB or IV accordingly to American Joint Committee on Cancer [AJCC] classification) - Male or female = 18 years old - Life expectancy of at least 12 weeks, in the opinion of the Investigator - Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 2 - Patients having: a) contributive biopsy performed on fresh tissue (FFPE blocks required) taken after progression on previous therapy showing: - presence of anaplastic lymphoma kinase (ALK) rearrangement, assessed by IHC and confirmed by FISH, - absence of resistance mechanism to alectinib assessed by the Biomarkers Board: 1. ALK I1151Tins I1171N/S, V1180L and G1202R mutations (known to induce a resistance to alectinib), 2. epidermal growth factor receptor (EGFR) exon 19 deletions, L858R mutation or Kirsten rat sarcoma viral oncogene homolog (KRAS) codon 12, 13 or 61 mutations, 3. High level of MET amplification, 4. tumor histologic transformation into small cell lung cancer. b) disease progression, limited to CNS without possibility of tissue biopsy, c) non-contributive molecular analyses (no enough tumor cells or DNA amount or failure of analyses for technical reasons): inclusion is at investigator discretion (his decision taken upon Biomarker Board recommendation) - History of crizotinib exposure - Adequate hematologic function - Adequate renal function - For all females of childbearing potential, a negative pregnancy test must be obtained within three days before starting study drug - 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 two adequate methods of contraception, including at least one method with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: - Prior therapy with other ALK inhibitors than crizotinib (including alectinib) - Patients with symptomatic CNS metastases who are neurologically unstable or require increasing doses of steroids within one week prior to Day 0 to manage CNS symptoms (Patients with brain or leptomeningeal metastases are allowed, symptomatic disease is allowed as long as symptoms are controlled and stable and prior treatment with whole brain radiation or gamma knife must have been completed at least 14 days prior to Day 0 and patients must be clinically stable) - Patients with progression limited to CNS and eligible to a focal treatment (surgery or stereotaxic radiotherapy) - Liver disease characterized by: Alanine transaminase (ALT) or aspartate aminotransferase (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 hepatitis - Patients with baseline QTc > 470 ms or patients with symptomatic bradycardia. - Pregnant or lactating women - Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the patient before trial entry - Serious, uncontrolled infections or current known infection with human immunodeficiency virus (HIV)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate Objective Response Rate (ORR) in all patients with measurable disease at baseline; Secondary Objective: Central Nervous System Objective Response Rate (C-ORR) in all patients with measurable CNS metastases at baseline. Progression-Free Survival (PFS) in all patients. Time to Progression in all patients. Disease Control Rate (DCR) in all patients with measurable disease. Duration Of Response (DOR) in all patients with measurable disease. CNS Duration Of Response (C-DOR) in all patients with measurable CNS metastases at baseline. Overall Survival (OS) rate at two-years in all patients. Time to CNS progression in all patients. Quality of life (QLQ-C30, LC13, BN20 questionnaires for patients with CNS metastases and EQ-5D-5L). ;Primary end point(s): ORR, defined as the percentage of patients who achieve complete response (CR) or partial response (PR) as determined by Investigators using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v.1.1);Timepoint(s) of evaluation of this end point: 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): C-ORR in all patients with measurable CNS metastases at baseline PFS in all patients TTP in all patients DCR in all patients DOR in all patients C-DOR in all patients Two-year OS Time to CNS progression ; Timepoint(s) of evaluation of this end point: C-ORR: 12 months PFS: 24 months TTP: 24 months DCR: 12 months DOR: 24 months C-DOR: 24 months OS: 24 months Time to CNS progression: 24 months | — |
Countries
France
Outcome results
None listed