None listed
Conditions
Interventions
Drug : This study is a phase II, single-arm, open label study. All participating patients must sign on the written informed consent form, and a separate form of consent will be used for the use of tis
Sponsors
Yonsei University Health System, Severance Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Subjects with histologically or cytologically confirmed, stage IV or recurrent NSCLC that carries a ROS1 rearrangement, as per anchored multiplex PCR ? ECOG performance status of 0 to 2 ? Male or female; = 20 years of age ? Subjects should be treatment naiive or may be allowed upto 2 prior systemic anti-cancer therapy for their stage IV or recurrent NSCLC, which includes cytotoxic chemotherapy and I-O, but excludes crizotinib. ? Subjects with measurable lesion (using RECIST 1.1 criteria) ? Subjects must have archival tissue sample available, collected either at the time of diagnosis of NSCLC or any time since ? Subjects who meet the following criteria: - Absolute neutrophil count (ANC) ?1.5 x 109/L - Platelet count?100 x 109/L - Serum creatinine ?1.5 x upper limit of normal (ULN) - AST (SGOT) and ALT (SGPT) ? 3 x upper limit of normal (ULN) (If there is Liver Metastasis ? 5 x upper limit of normal (ULN)) - Total bilirubin?1.5 x upper limit of normal (ULN) ? Provision of written informed consent prior to any study specific procedures ? Leptomeningeal carcinomatosis may be included
Exclusion criteria
Exclusion criteria: ? More than two actionable mutations ? Patients who received prior crizotinib therapy ? Any major operation or irradiation within 4 weeks of baseline disease assessment ? Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug ? Subjects with symptomatic central nervous system (CNS) metastases who are neurologically unstable or who have CNS complications that require urgent neurosurgical intervention(e.g. resection or shunt placement) ? Other co-existing malignancies or malignancies diagnosed within the last 3 years with the exception of basal cell carcinoma or cervical cancer in situ or treated thyroid cancer. ? Subjects with an uncontrolled major cardiovascular disease (including AMI within 12 months, unstable angina within 6 months, over NYHA class III congestive heart failure, congenital long QT syndrome, 2° or more AV Block and uncontrolled hypertension) ? Pregnant or lactating female ? Patients with known history of extensive disseminated bilateral interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and clinically significant radiation pneumonitis (i.e. affecting activities of daily living or requiring therapeutic intervention). ? Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with LDK378 and for the duration of participation (see Appendix 1 Tables): ? Medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (please refer to http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm) ? Strong inhibitors or strong inducers of CYP3A4/5 (please refer to http://medicine.iupui.edu/flockhart/table.htm or http://www.druginteractioninfo.org) ? Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, CYP2C8 and/or CYP2C9 (please refer to http://medicine.iupui.edu/flockhart/table.htm or http://www.druginteractioninfo.org) ? Therapeutic doses of warfarin sodium (Coumadin) or any other coumadin-derived anti-coagulant. Anticoagulants not derived from warfarin are allowed (eg, dabigatran, rivaroxaban, apixaban). ? Unstable or increasing doses of corticosteroids 16 enzyme-inducing anticonvulsive agents 17 herbal supplements 18 Patients who have received thoracic radiotherapy to lung fields = 4 weeks prior to starting the study treatment or patients who have not recovered from radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs), radiotherapy = 2 weeks prior to starting the study treatment or patients who have not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions = 2 weeks prior to starting study treatment is allowed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| overall response rate (ORR) | — |
Secondary
| Measure | Time frame |
|---|---|
| PFS,OS,DCR, safety profile, pharmacokinetics, identification of acquired resistance mechanism (optional) | — |
Countries
Korea, Republic of
Contacts
Public ContactYuri Kang
Yonsei University Health System, Severance Hospital
Outcome results
None listed