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Trial record 43 of 48 for:    Dovitinib

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

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ClinicalTrials.gov Identifier: NCT01443481
Recruitment Status : Completed
First Posted : September 29, 2011
Last Update Posted : June 8, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( 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.

Condition or disease Intervention/treatment Phase
Solid Tumors Hepatic Impairment Drug: Dovitinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-center, Open Label Study to Assess Pharmacokinetics of TKI258 in Adult Cancer Patients With Normal and Impaired Hepatic Function
Study Start Date : November 2011
Actual Primary Completion Date : October 2014
Actual Study Completion Date : October 2014

Arm Intervention/treatment
Experimental: TKI258 normal hepatic function
TKI258 Capsule, @ 500 mg p.o. o.d. 5 days on/2 days off
Drug: Dovitinib
Starting dose to be determined based on the study outcome of the mild and moderate hepatic impairment groups
Other Name: TKI258

Experimental: TKI258 mild hepatic impairment
TKI258 capsule @ 500 or 400 mg p.o. o.d. 5 days on/2 days off
Drug: Dovitinib
Starting dose to be determined based on the study outcome of the mild and moderate hepatic impairment groups
Other Name: TKI258

Experimental: TKI258 moderate hepatic impairment
TKI258 capsule @ starting dose at 400 mg p.o. o.d. 5 days on/2 days off
Drug: Dovitinib
Starting dose to be determined based on the study outcome of the mild and moderate hepatic impairment groups
Other Name: TKI258

Experimental: TKI258 severe hepatic impairment
TKI258 capsule Starting dose to be determined based on the study outcome of the mild and moderate hepatic impairment groups
Drug: Dovitinib
Starting dose to be determined based on the study outcome of the mild and moderate hepatic impairment groups
Other Name: TKI258




Primary Outcome Measures :
  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 Outcome Measures :
  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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01443481


Locations
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United States, California
University of California at Los Angeles Dept. of UCLA (4)
Los Angeles, California, United States, 90095
United States, North Carolina
Duke University Medical Center DUMC
Durham, North Carolina, United States, 27710
United States, Texas
Cancer Therapy & Research Center / UT Health Science Center SC
San Antonio, Texas, United States, 78229
Belgium
Novartis Investigative Site
Gent, Belgium, 9000
Germany
Novartis Investigative Site
Frankfurt, Germany, 60590
Novartis Investigative Site
Hannover, Germany, 30625
Italy
Novartis Investigative Site
Milano, MI, Italy, 20133
Novartis Investigative Site
Rozzano, MI, Italy, 20089
Novartis Investigative Site
Verona, VR, Italy, 37126
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands, 1066 CX
Novartis Investigative Site
Maastricht, Netherlands, 5800
Singapore
Novartis Investigative Site
Singapore, Singapore, 119228
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Additional Information:
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01443481     History of Changes
Other Study ID Numbers: CTKI258A2124
2011-000103-41 ( EudraCT Number )
First Posted: September 29, 2011    Key Record Dates
Last Update Posted: June 8, 2017
Last Verified: June 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
solid tumors
hepatic impairment
Child-Pugh classification
pharmacokinetics
PK
RECIST 1.1

Additional relevant MeSH terms:
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Liver Diseases
Digestive System Diseases