A phase I, multicenter, open-label dose escalation study of LDK378, administered orally in adult patients with tumors characterized by genetic abnormalities in anaplastic lymphoma kinase(ALK)
- Conditions
- Tumors with genetic abnormality in ALK10027655
- Registration Number
- NL-OMON36240
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 4
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 <= 5.58 mmol/l
- Platelets *100x109/L
- Total bilirubin * 1.5 x upper limit of normal (ULN)
- Alkaline phosphatase, AST (SGOT) and ALT (SGPT) * 2.5 x ULN, with liver metastasis *5 x ULN
- Creatinine * 1.5 x ULN or calculated creatinine clearance * 50 mL/min (* 0.835 mL/s)
- Amylase * ULN
- Lipase * ULN
- Fasting plasma glucose * 200 mg/dL (* 11.1 mmol/L)
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 (< 50 bpm)
- Corrected QTcF > 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 < 5x t1/2 or < 2 weeks (whichever is longer) prior to starting study drug . If prior treatment was crizotinib, LDK378 may start 2 weeks after the last dose.
10. Unresolved toxicity greater than CTCAE grade 1 from previous anti-cancer therapy or radiotherapy (excluding neurotoxicity, alopecia, ototoxicity, lymphopenia)
11. Radiotherapy * 3 weeks
12. Major surgery * 2 weeks
13. Strong inhibitors or inducers of CYP3A4/5
14. CYP2C9: warfarin and phenytoin
15. Coumarin-type anticoagulants. Treatment with maximum daily dose of 2 mg of coumarin-type anticoagulants for line patency is permitted. Low molecular weight heparin is permitted.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary: Incidence rate of Dose Limiting Toxicities (DLT) during the first<br /><br>cycle including PK run-in.</p><br>
- Secondary Outcome Measures
Name Time Method <p>* Adverse drug reactions and serious adverse drug reactions, changes in<br /><br>hematology and blood chemistry values, assessments of physical examinations,<br /><br>vital signs and electrocardiograms.<br /><br>* Plasma concentration of LDK378 and PK parameters.<br /><br>* Overall response (complete response (CR) or partial response (PR)) rate<br /><br>defined according to RECIST.</p><br>