Pharmacokinetics (PK) of TKI258 in Cancer Patients With Normal and Impaired Hepatic Function
- Registration Number
- NCT01443481
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 38
- Patients with histologically or cytologically confirmed solid tumor, excluding breast cancer, that is either refractory to the standard therapy or has no available therapies.
- ECOG performance status (PS) 0 or 1
- Patients must have measurable and/or non-measurable lesion(s) as assessed by Computer Tomography (CT) Scan or Magnetic Resonance Imaging (MRI) per RECIST 1.1
- Patients with known brain metastases.
- Patients who have undergone major surgery ≤ 4 weeks prior to starting study treatment
Other protocol-defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description TKI258 normal hepatic function Dovitinib TKI258 Capsule, @ 500 mg p.o. o.d. 5 days on/2 days off TKI258 moderate hepatic impairment Dovitinib TKI258 capsule @ starting dose at 400 mg p.o. o.d. 5 days on/2 days off TKI258 mild hepatic impairment Dovitinib TKI258 capsule @ 500 or 400 mg p.o. o.d. 5 days on/2 days off TKI258 severe hepatic impairment Dovitinib TKI258 capsule Starting dose to be determined based on the study outcome of the mild and moderate hepatic impairment groups
- Primary Outcome Measures
Name Time Method Pharmacokinetic (PK) parameter of Tmax following a single dose of TKI258 and at the steady state Day 1, Day 19 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).
Pharmacokinetic (PK) parameter of Cmax following a single dose of TKI258 and at the steady state Day 1, Day 19 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).
Pharmacokinetic (PK) parameter of AUClast following a single dose of TKI258 and at steady state Day 1, Day 19 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)
Pharmacokinetic (PK) parameter of AUCinf following a single dose of TKI258 Day 1, Day 19 AUCinf is the time to zero to infinity (mass x time x volume)
- Secondary Outcome Measures
Name Time Method Change from Baseline in Vital Signs Baseline, Weeks 1, 4, 5, 9 and once every 8 weeks thereafter 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.
Best overall response to anti-tumor activity of TKI258 through imaging as per RECIST 1.1 Every 8 weeks 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.
Pharmacokinetics and Hepatic Function Abnormalities Baseline, every 4 weeks 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.
Frequency of Adverse Events and Serious Adverse Events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) Baseline and every 4 weeks 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.
Change from Baseline in Electrocardiogram Baseline, Weeks 1, 4, 5 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.
Trial Locations
- Locations (4)
University of California at Los Angeles Dept. of UCLA (4)
🇺🇸Los Angeles, California, United States
Duke University Medical Center DUMC
🇺🇸Durham, North Carolina, United States
Cancer Therapy & Research Center / UT Health Science Center SC
🇺🇸San Antonio, Texas, United States
Novartis Investigative Site
🇸🇬Singapore, Singapore