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

Novartis

Status and phase: Completed; Phase 1

Conditions: Hepatic Impairment; Solid Tumors

Treatments: Drug: Dovitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01443481

2011-000103-41 (EudraCT Number)

CTKI258A2124

Details and patient eligibility

About

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.

Enrollment: 38 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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38 participants in 4 patient groups

TKI258 normal hepatic function

Experimental group

Description:

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

Treatment:

Drug: Dovitinib

TKI258 mild hepatic impairment

Experimental group

Description:

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

Treatment:

Drug: Dovitinib

TKI258 moderate hepatic impairment

Experimental group

Description:

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

Treatment:

Drug: Dovitinib

TKI258 severe hepatic impairment

Experimental group

Description:

TKI258 capsule Starting dose to be determined based on the study outcome of the mild and moderate hepatic impairment groups

Treatment:

Drug: Dovitinib