Clinical trial NCT01443481: Pharmacokinetics (PK) of TKI258 in Cancer Patients With Normal and Impaired Hepatic Function
Official title: A Multi-center, Open Label Study to Assess Pharmacokinetics of TKI258 in Adult Cancer Patients With Normal and Impaired Hepatic Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Hepatic Impairment
Keywords: solid tumors
hepatic impairment
Child-Pugh classification
pharmacokinetics
PK
RECIST 1.1
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-09-29
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetic (PK) parameter of Cmax following a single dose of TKI258 and at the steady state
timeFrame: Day 1, Day 19
measure: Pharmacokinetic (PK) parameter of Tmax following a single dose of TKI258 and at the steady state
timeFrame: Day 1, Day 19
measure: Pharmacokinetic (PK) parameter of AUClast following a single dose of TKI258 and at steady state
timeFrame: Day 1, Day 19
measure: Pharmacokinetic (PK) parameter of AUCinf following a single dose of TKI258
timeFrame: Day 1, Day 19
Secondary outcomes:
measure: Frequency of Adverse Events and Serious Adverse Events as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: Baseline and every 4 weeks
measure: Change from Baseline in Vital Signs
timeFrame: Baseline, Weeks 1, 4, 5, 9 and once every 8 weeks thereafter
measure: Best overall response to anti-tumor activity of TKI258 through imaging as per RECIST 1.1
timeFrame: Every 8 weeks
measure: Change from Baseline in Electrocardiogram
timeFrame: Baseline, Weeks 1, 4, 5
measure: Pharmacokinetics and Hepatic Function Abnormalities
timeFrame: Baseline, every 4 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California at Los Angeles Dept. of UCLA (4)
state: California
city: Durham
country: United States
facility: Duke University Medical Center DUMC
state: North Carolina
city: San Antonio
country: United States
facility: Cancer Therapy & Research Center / UT Health Science Center SC
state: Texas
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Verona
country: Italy
facility: Novartis Investigative Site
state: VR
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Maastricht
country: Netherlands
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: