Solid TumorsPhase 1NCT01443481
Pharmacokinetics (PK) of TKI258 in Cancer Patients With Normal and Impaired Hepatic Function
A Phase 1 study testing Dovitinib in people with Solid Tumors and Hepatic Impairment, run by Novartis Pharmaceuticals at 12 sites in 6 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Hepatic Impairment
- What is being tested?
- Dovitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 12 sitesin 6 countries
- Study dates
- Nov 2011to Oct 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
12 sites in 6 countries.
12 sites in 6 countries
United States3 sites
Duke University Medical Center DUMC
Durham, North Carolina, 27710
University of California at Los Angeles Dept. of UCLA (4)
Los Angeles, California, 90095
Cancer Therapy & Research Center / UT Health Science Center SC
San Antonio, Texas, 78229
Italy3 sites
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Rozzano, MI, 20089
Novartis Investigative Site
Verona, VR, 37126
Germany2 sites
Novartis Investigative Site
Frankfurt, 60590
Novartis Investigative Site
Hanover, 30625
Netherlands2 sites
Novartis Investigative Site
Amsterdam, 1066 CX
Novartis Investigative Site
Maastricht, 5800
About this study
Official title: 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.
- Conditions
- Solid Tumors, Hepatic Impairment
- Being tested
- Dovitinib
- Keywords
- solid tumors, hepatic impairment, Child-Pugh classification, pharmacokinetics, PK, RECIST 1.1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DovitinibDrug
Also called TKI258
Starting dose to be determined based on the study outcome of the mild and moderate hepatic impairment groups
| Study group | Role | What they receive |
|---|---|---|
| TKI258 normal hepatic function | Experimental | TKI258 Capsule, @ 500 mg p.o. o.d. 5 days on/2 days off Receives: Drug: Dovitinib |
| TKI258 mild hepatic impairment | Experimental | TKI258 capsule @ 500 or 400 mg p.o. o.d. 5 days on/2 days off Receives: Drug: Dovitinib |
| TKI258 moderate hepatic impairment | Experimental | TKI258 capsule @ starting dose at 400 mg p.o. o.d. 5 days on/2 days off Receives: Drug: Dovitinib |
| TKI258 severe hepatic impairment | Experimental | TKI258 capsule Starting dose to be determined based on the study outcome of the mild and moderate hepatic impairment groups Receives: Drug: Dovitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Day 1, Day 19
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).
Measured: Day 1, Day 19
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)
Measured: Day 1, Day 19
Pharmacokinetic (PK) parameter of AUCinf following a single dose of TKI258
AUCinf is the time to zero to infinity (mass x time x volume)
Measured: Day 1, Day 19
Secondary outcomes (5)
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.
Measured: Baseline and every 4 weeks
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.
Measured: 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
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.
Measured: Every 8 weeks
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.
Measured: Baseline, Weeks 1, 4, 5
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.
Measured: Baseline, every 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2011 (estimated)
- Study startNov 2011
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01443481
- Sponsor's protocol ID
- CTKI258A2124
- Other IDs
- 2011-000103-41
- Status last verified
- Jun 2017
- First submitted
- 17 Sep 2011
- Last updated
- 21 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Open Label Study to Assess Pharmacokinetics of TKI258 in Adult Cancer Patients With Normal and Impaired Hepatic Function
- ClinicalTrials.gov ID
- NCT01443481
- Acronym / sponsor ID
- CTKI258A2124
- Conditions
- Solid Tumors, Hepatic Impairment
- Keywords
- solid tumors, hepatic impairment, Child-Pugh classification, pharmacokinetics, PK, RECIST 1.1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 29 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| TKI258 normal hepatic function | Experimental | Drug: DovitinibTKI258 Capsule, @ 500 mg p.o. o.d. 5 days on/2 days off |
| TKI258 mild hepatic impairment | Experimental | Drug: DovitinibTKI258 capsule @ 500 or 400 mg p.o. o.d. 5 days on/2 days off |
| TKI258 moderate hepatic impairment | Experimental | Drug: DovitinibTKI258 capsule @ starting dose at 400 mg p.o. o.d. 5 days on/2 days off |
| TKI258 severe hepatic impairment | Experimental | Drug: DovitinibTKI258 capsule Starting dose to be determined based on the study outcome of the mild and moderate hepatic impairment groups |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DovitinibAlso: TKI258Starting dose to be determined based on the study outcome of the mild and moderate hepatic impairment groups | Drug | TKI258 mild hepatic impairment, TKI258 moderate hepatic impairment, TKI258 normal hepatic function, TKI258 severe hepatic impairment |
Primary outcome
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).
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).
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)
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)
5 secondary outcomes
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
Change from Baseline in Vital Signs
Time frame: 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
Change from Baseline in Electrocardiogram
Time frame: Baseline, Weeks 1, 4, 5
Pharmacokinetics and Hepatic Function Abnormalities
Time frame: Baseline, every 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2020.
- Results for CTKI258A2124 from the Novartis Clinical Trials websiteLink provided by the sponsor.
Related trials for Solid Tumors
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A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
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A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
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IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
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Malignant Solid Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
12 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dovitinib in people with Solid Tumors and Hepatic Impairment, run by Novartis Pharmaceuticals at 12 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Italy, Germany, Netherlands, Belgium and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetic (PK) parameter of Cmax following a single dose of TKI258 and at the steady state (time frame: Day 1, Day 19). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2020.