Non-small cell lung cancer
Conditions
Interventions
A treatment cycle is defined as 28 days from the start of LDK378. 750 mg of LDK378 is orally administered once daily. After preoperative induction treatment with LDK378 for 3 cycles, surgical resectio
Sponsors
National Cancer Center HospitalEast
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Histologically or cytologically confirmed diagnosis of NSCLC. 2)ALK fusion gene is determined to be positive by at least 2 of the following methods: FISH, immunohistochemical (IHC) examination, and RT-PCR . 3)Clinical stage is II or III 4)It is considered that complete tumor removal can be achieved by pneumonectomy (lobectomy or more extensive surgical resection) and by lymph node dissection. 5)Predicted residual FEV1 after resection is >= 800 ml. 6)No previous treatment. 7) Male or female aged 20 years and over. 8)Performance status (ECOG) is 0 or 1. 9) At least one measurable lesion as defined by RECIST (Response Evaluation Criteria in Solid Tumor) ver1.1. 10)The following laboratory values indicative of adequate organ functions are available within 7 days before registration: a. Neutrophil count >= 1,500/mm3 b. Platelet count >= 100,000/mm3 c. Hemoglobin (Hgb) >= 10.0 g/dL d. Serum albumin >= 3.0 g/dL e. Creatinine clearance >= 30 mL/min f. Total bilirubin <= 1.5 mg/dL (total bilirubin <= 3.0 mg/dL in patients with Gilbert's syndrome) g. AST (SGOT) <= 100 IU/L h. ALT (SGPT) <= 100 IU/L i. ALP <= 1800 IU/L j. Amylase <= 300 U/L k. Lipase <= 57U/L l. Fasting plasma glucose <= 175 mg/dL ( <= 9.8 nmol/L) m. Potassium <= 5.0 mEq/L n. Magnesium <= 10.0 mg/dL o. Phosphorus <= 4.5 mg/dL p. Calcium <= 10.0 mg/dL q. SpO2 >= 93% 11)Women of child-bearing-potential show a negative result of pregnancy test conducted within 7 days before registration. Both male and female patients agree to use an appropriate method of contraception during the study and for 3 months after discontinuation of the study drug. 12)Patients expected to survive for at least 3 months after the first day of preoperative chemotherapy. 13)Patients intended and able to comply with scheduled study visit, treatment plan, laboratory tests, and other study-related procedures.
Exclusion criteria
Exclusion criteria: 1) Patient with lymph node metastasis in the neck/ lymph node metastasis in the supraclavicular/ contralateral hilus and contralateral mediastinum. 2) Patient having previously experienced hypersensitivity to any additive of LDK378. 3) Patient with a history of or currently having malignant tumors other than NSCLC. 4) Patient with a history of interstitial lung disease or interstitial pneumonia. 5) Patient with any of the following clinically significant and poorly controlled heart diseases: -Unstable angina pectoris and Myocardial infarction within 6 months before registration -A history of congestive heart failure -Poorly controlled hypertension defined as systolic blood pressure >= 160 mmHg or diastolic blood pressure >= 100 mmHg -Arrhythmia not controlled with drugs -QT interval > 470 msec on ECG 6) Patient with poorly controlled diabetes mellitus. 7) Patient receiving any of the following drugs and in whom it is impossible to discontinue them for at least 1 week before the start of treatment with LDK378: -Potent CYP3A4/5 inhibitor or inducer -Drugs with a small therapeutic index that are mainly metabolized by CYP3A4/5, CYP2C8 or CYP2C9 -Drugs known to prolong QT interval or induce Torsades de pointes 8) Patient receiving warfarin sodium or other coumarin anticoagulants. 9) Patient treated with corticosteroids at unstable doses. 10) Patient receiving enzyme-inducing anticonvulsants and in whom it is impossible to discontinue them for at least 1 week before the first administration of LDK378. 11) Pregnant women or breast-feeding women. 12) Patients with any major acute or chronic medical or mental condition or laboratory abnormality that is considered to increase the risk associated with participation in the study by the investigator. 14) Functional gastrointestinal tract disorder/ gastrointestinal disease that significantly prevents absorption of LDK378. 15) Patient has a history of pancreatitis/ increased amylase or lipase that was due to pancreatic disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Major pathological response rate | — |
Secondary
| Measure | Time frame |
|---|---|
| ?Incidence of adverse events ?Relapse-free survival: RFS ?Overall survival: OS ?Response rate: RR ?Pathological complete response rate: pCR rate ?Operability ?Complete resection rate | — |
Countries
Japan
Outcome results
None listed