A Study of LDK378 in Patients With Non-small Cell Lung Cancer Harboring ROS1 Rearrangement

This is an interventional treatment trial for Non-small Cell Lung Cancer Harboring ROS1 Rearrangement focused on measuring NSCLC, ROS1 rearrangement, Ceritinib, LDK378 Read More

Inclusion criteria

• 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
• treatment naive or may be allowed up to 2 prior systemic anti-cancer therapy for their stage IV or recurrent NSCLC, which includes cytotoxic chemotherapy and I-O, but excludes crizotinib.
• measurable lesion (using RECIST 1.1 criteria)
• measurable lesion (using RECIST 1.1 criteria)
• archival tissue sample available, collected either at the time of diagnosis of NSCLC or any time since

• Subjects who meet the following criteria:

  • ANC 1.5 x 109/L -Platelet 100 x 109/L
  • creatinine 1.5 x ULN
  • AST (SGOT) and ALT (SGPT) 3 x ULN (If there is Liver Metastasis 5 x ULN
  • Total bilirubin 1.5 x ULN
• written informed consent prior to any study specific procedures
• Leptomeningeal carcinomatosis may be included

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
• enzyme-inducing anticonvulsive agents
• herbal supplements
• 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.