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

Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01443481
• Other study ID #: CTKI258A2124
• Secondary ID: 2011-000103-41
• Status: Completed
• Phase: Phase 1
• Start date: November 2011
• Est. completion date: October 2014

Study information

• Verified date: June 2017
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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/exclusion criteria may apply

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases
• Solid Tumors

Intervention

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

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Gent
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Hannover
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Rozzano	MI
Italy	Novartis Investigative Site	Verona	VR
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Maastricht
Singapore	Novartis Investigative Site	Singapore
United States	Duke University Medical Center DUMC	Durham	North Carolina
United States	University of California at Los Angeles Dept. of UCLA (4)	Los Angeles	California
United States	Cancer Therapy & Research Center / UT Health Science Center SC	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Italy,  Netherlands,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Day 1, Day 19
Primary	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).	Day 1, Day 19
Primary	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)	Day 1, Day 19
Primary	Pharmacokinetic (PK) parameter of AUCinf following a single dose of TKI258	AUCinf is the time to zero to infinity (mass x time x volume)	Day 1, Day 19
Secondary	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.	Baseline and every 4 weeks
Secondary	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.	Baseline, Weeks 1, 4, 5, 9 and once every 8 weeks thereafter
Secondary	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.	Every 8 weeks
Secondary	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.	Baseline, Weeks 1, 4, 5
Secondary	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.	Baseline, every 4 weeks

External Links

•   Results for CTKI258A2124 from the Novartis Clinical Trials website