An open-label, multicenter, phase II study of CERITINIB in patients with non-small cell lung cancer harboring ROS1 rearrangement
- Conditions
- Neoplasms
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 46
? 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
? 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.
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method overall response rate (ORR)
- Secondary Outcome Measures
Name Time Method PFS,OS,DCR, safety profile, pharmacokinetics, identification of acquired resistance mechanism (optional)