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

NCT01443481 | Completed Phase 1

• 2 other identifiers: CTKI258A21242011-000103-41
• Study Type: interventional
• Target: 38
• Locations: 6 countries
• Sites: 12

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.

Conditions

Solid Tumors; Hepatic Impairment

Keywords

solid tumors; hepatic impairment; Child-Pugh classification; pharmacokinetics; PK; RECIST 1.1

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (5)

• Frequency of Adverse Events and Serious Adverse Events as assessed by Common Terminology Criteria for Adverse Events (CTCAE)

  Baseline and every 4 weeks

• Change from Baseline in Vital Signs

  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

  Every 8 weeks

• Change from Baseline in Electrocardiogram

  Baseline, Weeks 1, 4, 5

• Pharmacokinetics and Hepatic Function Abnormalities

  Baseline, every 4 weeks

Study Arms (4)

TKI258 normal hepatic function

EXPERIMENTAL

TKI258 Capsule, @ 500 mg p.o. o.d. 5 days on/2 days off

Drug: Dovitinib

TKI258 mild hepatic impairment

EXPERIMENTAL

TKI258 capsule @ 500 or 400 mg p.o. o.d. 5 days on/2 days off

Drug: Dovitinib

TKI258 moderate hepatic impairment

EXPERIMENTAL

TKI258 capsule @ starting dose at 400 mg p.o. o.d. 5 days on/2 days off

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

Drug: Dovitinib

Interventions

Dovitinib DRUG

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

Also known as: TKI258

TKI258 mild hepatic impairment; TKI258 moderate hepatic impairment; TKI258 normal hepatic function; TKI258 severe hepatic impairment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Patients with known brain metastases.
• Patients who have undergone major surgery ≤ 4 weeks prior to starting study treatment

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

University of California at Los Angeles Dept. of UCLA (4)

Los Angeles, California, 90095, United States

Location

Duke University Medical Center DUMC

Durham, North Carolina, 27710, United States

Location

Cancer Therapy & Research Center / UT Health Science Center SC

San Antonio, Texas, 78229, United States

Location

Novartis Investigative Site

Ghent, 9000, Belgium

Location

Novartis Investigative Site

Frankfurt, 60590, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Verona, VR, 37126, Italy

Location

Novartis Investigative Site

Amsterdam, 1066 CX, Netherlands

Location

Novartis Investigative Site

Maastricht, 5800, Netherlands

Location

Novartis Investigative Site

Singapore, 119228, Singapore

Location

Related Links

• Results for CTKI258A2124 from the Novartis Clinical Trials website

MeSH Terms

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2011
• First Posted: September 29, 2011
• Study Start: November 1, 2011
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: December 21, 2020

Record last verified: 2017-06

Locations

SG (1); DE (2); US (3); BE (1); IT (3); NL (2)