Tumors with genetic abnormality in ALK
Conditions
Interventions
Investigational drug: LDK378, available in 25mg, 50 mmg and 100mg capsules.
LDK378 will be administered orally as a continuous daily dosing.
Starting dose will be 50 mg/day.
Sponsors
Novartis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Patients with tumors characterized by abnormalities in ALK (translocation or mutation). 2. ECOG performance status * 2 3. Laboratory: -Absolute Neutrophil Count *1.5x109/L - Hemoglobin * 9 g/dl
Exclusion criteria
Exclusion criteria: 1. Central nervous system (CNS) metastases which are unstable, symptomatic and require increasing doses of steroids to control the disease. 2. Unresolved nausea, vomiting or diarrhea > CTCAE grade 1 3. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of LDK378 4. History of pancreatitis or history of increased amylase or lipase 5. Acute or chronic liver disease. Evidence of previous hepatitis viral infection (testing is not mandatory) 6. Clinically significant cardiac disease including congestive heart failure (New York Heart Association Class III or IV), arrhythmia or conduction abnormality requiring medication, or cardiomyopathy; or clinically uncontrolled hypertension (blood pressure > 160/110 mmHg) 7. Impaired cardiac function, including: - Complete left bundle branch block - Cardiac pacemaker - Congenital long QT syndrome - History or presence of ventricular tachyarrhythmia - Presence of unstable atrial fibrillation (ventricular response > 100 bpm - Clinically significant resting bradycardia ( 450 msec for males and > 470 msec for females at screening - PR * 240 msec and QRS * 110 msec - Right bundle branch block + left anterior hemiblock (bifascicular block) - Angina pectoris and Acute Myocard Infarction * 3 months prior to starting study drug 8. Other concurrent severe and/or uncontrolled medical conditions 9. Prior treatment with chemotherapy or biologic therapy or other investigational agent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary: Incidence rate of Dose Limiting Toxicities (DLT) during the first cycle including PK run-in. | — |
Secondary
| Measure | Time frame |
|---|---|
| * Adverse drug reactions and serious adverse drug reactions, changes in hematology and blood chemistry values, assessments of physical examinations, vital signs and electrocardiograms. * Plasma concentration of LDK378 and PK parameters. * Overall response (complete response (CR) or partial response (PR)) rate defined according to RECIST. | — |
Countries
Netherlands
Outcome results
None listed