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

December 17, 2020 updated by: Novartis Pharmaceuticals

A Multi-center, Open Label Study to Assess Pharmacokinetics of TKI258 in Adult 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
38

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • TKI258

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
Day 1, Day 19
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).
Day 1, Day 19
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)
Day 1, Day 19
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)
Day 1, Day 19

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Baseline and every 4 weeks
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.
Baseline, Weeks 1, 4, 5, 9 and once every 8 weeks thereafter
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.
Every 8 weeks
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.
Baseline, Weeks 1, 4, 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.
Baseline, every 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 17, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 28, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 29, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 21, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 17, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CTKI258A2124
  • 2011-000103-41 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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