Skip to main content
OpenTrials
Completed

NCT Number: NCT01443481

Pharmacokinetics (PK) of TKI258 in Cancer Patients With Normal and Impaired Hepatic Function

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Solid Tumors Hepatic Impairment

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site, Ghent, Belgium

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

dovitinib

Drug

Starting dose to be determined based on the study outcome of the mild and moderate hepatic impairment groups

Other names: TKI258

Primary outcomes

  1. Pharmacokinetic (PK) parameter of Cmax following a single dose of TKI258 and at the steady state

    Time frame: 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).

  2. Pharmacokinetic (PK) parameter of Tmax following a single dose of TKI258 and at the steady state

    Time frame: 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).

  3. Pharmacokinetic (PK) parameter of AUClast following a single dose of TKI258 and at steady state

    Time frame: 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)

  4. Pharmacokinetic (PK) parameter of AUCinf following a single dose of TKI258

    Time frame: Day 1, Day 19

    AUCinf is the time to zero to infinity (mass x time x volume)

Secondary outcomes

  1. Frequency of Adverse Events and Serious Adverse Events as assessed by Common Terminology Criteria for Adverse Events (CTCAE)

    Time frame: 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.

  2. Change from Baseline in Vital Signs

    Time frame: 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.

  3. Best overall response to anti-tumor activity of TKI258 through imaging as per RECIST 1.1

    Time frame: 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.

  4. Change from Baseline in Electrocardiogram

    Time frame: 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.

  5. Pharmacokinetics and Hepatic Function Abnormalities

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Multi-center, Open Label Study to Assess Pharmacokinetics of TKI258 in Adult Cancer Patients With Normal and Impaired Hepatic Function

Important dates

Study start
2011
Primary completion
2014
Study completion
2014
First posted
Sep 29, 2011
Registry last updated
Dec 21, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.