A Phase 1 interventional study of Dovitinib in Solid Tumors and Hepatic Impairment, sponsored by Novartis Pharmaceuticals. Completed at 12 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-12-21.
Sponsored by Novartis Pharmaceuticals · Phase 1, Interventional, and Treatment
This is a multi-center, open label study to assess pharmacokinetics (PK) of TKI258 at single-dose and steady state in adult cancer patients either with mild, moderate or severe hepatic impairment or with normal hepatic function. Hepatic function in study patients will be categorized as normal, mild, moderate or severe based upon pre-dose (Day 1) total bilirubin and AST/ALT levels. Starting dose of TKI258 will depend on total bilirubin and ALT/AST levels at baseline. Patients will be treated until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death or discontinuation from the study treatment for any other reason.
2,081 studies on the registry are indexed under Liver Diseases; 390 are open to participants now.
This study's enrollment of 38 is below the median of 50 across 1,323 interventional studies indexed under Liver Diseases.
Browse Liver Diseases studies →Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.
Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.
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Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply
TKI258 Capsule, @ 500 mg p.o. o.d. 5 days on/2 days off
Drug: Dovitinib
TKI258 capsule @ 500 or 400 mg p.o. o.d. 5 days on/2 days off
Drug: Dovitinib
TKI258 capsule @ starting dose at 400 mg p.o. o.d. 5 days on/2 days off
Drug: Dovitinib
TKI258 capsule Starting dose to be determined based on the study outcome of the mild and moderate hepatic impairment groups
Drug: Dovitinib
Starting dose to be determined based on the study outcome of the mild and moderate hepatic impairment groups
Also known as: TKI258
Pharmacokinetic (PK) parameter of Cmax following a single dose of TKI258 and at the steady state
Cmax will be evaluated after a single dose of TKI258 and at the steady state following a 5 days on/2 days off dosing schedule. Cmax is the maximum (peak) plasma, blood, serum, or other body fluid drug concentration after a single dose administration (mass x volume - 1).
Time frame: Day 1, Day 19
Pharmacokinetic (PK) parameter of Tmax following a single dose of TKI258 and at the steady state
Tmax will be evaluated after a single dose of TKI258 and at the steady state following a 5 days on/2 days off dosing schedule. Tmax is the time to to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after a single dose administration (mass x volume - 1).
Time frame: Day 1, Day 19
Pharmacokinetic (PK) parameter of AUClast following a single dose of TKI258 and at steady state
AUClast will be evaluated after a single dose of TKI258 and at the steady state following a 5 days on/2 days off dosing schedule. AUC from time zero to the last measurable concentration sampling time t(last) (mass x time x volume\^-1)
Time frame: Day 1, Day 19
Pharmacokinetic (PK) parameter of AUCinf following a single dose of TKI258
AUCinf is the time to zero to infinity (mass x time x volume)
Time frame: Day 1, Day 19
Frequency of Adverse Events and Serious Adverse Events as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
The Common Terminology Criteria for Adverse Events (AE) is a descriptive terminology which can be utilized for AE reporting. An AE is any unfavorable and unintended sign (including an abnormal laboratory finding),symptom, or disease temporally associated with the use of a treatment.
Time frame: Baseline and every 4 weeks
Change from Baseline in Vital Signs
Body temperature, sitting pulse rate, and sitting blood pressure will be measured at each visit. Blood Pressure (BP) will be measured according to the National Institute of Health, National Hart, Lung and Blood Institute Guidelines with following standardized techniques: patients are seated; BP measurement begins after at least 5 minutes of rest, the appropriate cuff size is used , measurements will be taken preferably with a mercury sphygmomanometer. If the BP reading is ≥ 160mm Hg systolic and/or ≥100 mmHg diastolic, repeat the measurement to verify initial reading.
Time frame: Baseline, Weeks 1, 4, 5, 9 and once every 8 weeks thereafter
Best overall response to anti-tumor activity of TKI258 through imaging as per RECIST 1.1
RECIST (Response Evaluation Criteria In Solid Tumors) is a set of published rules that define when cancer patients improve ("respond"), stay the same ("stable") or worsen ("progression") during treatments.
Time frame: Every 8 weeks
Change from Baseline in Electrocardiogram
A standard 12 lead Electrocardiogram(ECG)will be used. In order for an accurate evaluation of baseline QTc, a total of three 12-lead ECGs will be performed within 72 hours prior to the first dose of TKI258 administration on Week 1, Day 1. All ECGs will be transmitted to a central laboratory and will be centrally reviewed by an independent reviewer.
Time frame: Baseline, Weeks 1, 4, 5
Pharmacokinetics and Hepatic Function Abnormalities
Exploration of the relationship between Pharmacokinetics (PK) and hepatic functional abnormalities (i.e. bilirubin, ALT/AST, and Child-Pugh classification using regression analysis as appropriate.
Time frame: Baseline, every 4 weeks
This study is completed, as verified in Jun 2017. You cannot join it, but the record below documents what was studied.
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Novartis Pharmaceuticals