Hepatic Impairment, Solid Tumors
Conditions
Keywords
solid tumors, hepatic impairment, Child-Pugh classification, pharmacokinetics, PK, RECIST 1.1
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.
Interventions
DRUGDovitinib
Starting dose to be determined based on the study outcome of the mild and moderate hepatic impairment groups
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with histologically or cytologically confirmed solid tumor, excluding breast cancer, that is either refractory to the standard therapy or has no available therapies. 2. ECOG performance status (PS) 0 or 1 3. 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
Exclusion criteria
1. Patients with known brain metastases. 2. Patients who have undergone major surgery ≤ 4 weeks prior to starting study treatment Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 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 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Belgium, Germany, Italy, Netherlands, Singapore, United States
Outcome results
None listed