Advanced non-small-cell lung cancer harboring a RET fusion gene
Conditions
Interventions
Administration of CH5424802 (600 mg bid, 450 mg bid, or 300 mg bid) in a cycle of 21 days will continue until criteria for a respite, dosage reduction, or discontinuation of the protocol treatment are
Sponsors
Cancer Research Institute, Kanazawa University
CHUGAI PHARMACEUTICAL CO., LTD.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent 2. Age 20 or older 3. Histologically or cytologically diagnosed NSCLC 4. Unresectable locally advanced or metastatic disease 5. Tumor samples test positive for a RET fusion gene 6. Testing negative for an EGFR mutation 7. Testing negative for an ALK fusion gene 8. Failure to respond to a course or multiple courses of chemotherapy or progression of NSCLC a course or multiple courses of chemotherapy 9. Life expectancy of 3 months or longer 10. ECOG Performance status of 0-2 11. Female patients of childbearing potential test negative for pregnancy during screening 12. Having adequate bone marrow, liver, renal, and respiratory function 1)Neutrophil count: 1,500/mm3 or higher 2)Hemoglobin: 9.0 g/dL or higher 3)Platelet count: 100,000/mm3 or higher 4)Serum creatinine: 1.5 mg/dL or less 5)ALT, AST, and ALP: Levels 3 times or less the upper limit of normal (local laboratory reference values) 6)Serum bilirubin: Level 1.5 times or less the upper limit of normal (local laboratory reference values) 7)SpO2: 92% or higher 13.Only for Step 2 having one or more measurable lesions in accordance with the revised RECIST guidelines (version 1.1)
Exclusion criteria
Exclusion criteria: 1.Having previously received alectinib 2.A history of hypersensitivity to additives contained in CH5424802 3.Having an infection requiring systemic administration of antibiotics or antivirals 4.Laboratory results positive for HBs antigen or anti-HCV antibodies 5.Unstable brain metastases or spinal cord compression that requires treatment 6.A condition that would preclude receipt of the study treatment 7.A QTc interval greater than 480 msec, a history of long QT syndrome, a history of clinically significant ventricular arrhythmia, currently receiving antiarrhythmic drugs, or having an implanted defibrillator 8.Interstitial lung disease or a history of that disease. 9.Poorly controlled diabetes 10.Hypertension that cannot be managed with medication 11.Female patients who are or may be pregnant 12.Patients who would have difficulty taking medication orally 13.Exhibiting adverse reactions prior to treatment that remain Grade 2 or more severe 14.If the following times have not elapsed from prior to treatment or the conclusion of treatment upon enrollment in this study 1)Surgery or radiation therapy: 4 wks 2)Bronchoscopic treatment: 2 wks 3)Chemotherapy: 4 wks 4)Lenvatinib or vandetanib: 3 wks 5)Nitrosourea or MMC: 6 wks 6)Endocrine therapy or immunotherapy: 2 wks 7)Transfusion or a hematopoietic growth factor: 2 wks 8)Other trial medications: 4 wks 15.Patients with pleural effusion, pericardial effusion, or ascites requiring treatment. This does not apply if, upon enrollment, 2 or more wks have passed since fluid was drained and effusion/ascites has not worsened. 16.Patients with a deep vein thrombus or pulmonary thromboembolism that requires treatment 17.Patients with multiple malignancies with differing histologies. Or patients with a history of those malignancies in the past 5 years. 18.Patients whom an investigator or sub-investigator deems ineligible for participation in this study for some other reason.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| [Step 1] 1) Dose-limiting toxicity (DLT) 2) Safety 3) Pharmacokinetic parameters [Step 2] Objective response rate in RET-tyrosine kinase inhibitor (TKI)-naive patients according to a central review | — |
Secondary
| Measure | Time frame |
|---|---|
| [Step 1] 1) Objective response rate in RET-TKI-naive patients according to a central review 2) Response rate according to a review by investigators or sub-investigators 3) Progression-free survival 4) Disease control rate 5) Overall survival 6) Response rate in patients previously treated with RET-TKIs 7) Efficacy in patients harboring different forms of the RET fusion gene [Step 2] 1) Response rate according to a review by investigators or sub-investigators 2) Safety 3) Pharmacokinetic parameters 4) Progression-free survival 5) Disease control rate 6) Overall survival 7) Response rate in patients previously treated with RET-TKIs 8) Efficacy in patients harboring different forms of the RET fusion gene | — |
Countries
Japan
Contacts
Public ContactShinji Takeuchi
Kanazawa University Hospital Cancer Center
Outcome results
None listed