Pharmacokinetic Drug-drug Interaction Study of Dovitinib (TKI258) in Patients With Advanced Solid Tumors

Novartis

Status and phase

Completed

Phase 1

Conditions

Advanced Solid Tumors, Excluding Breast Cancer

Treatments

Drug: midazolam

Drug: diclofenac

Drug: omeprazole

Drug: caffeine

Drug: TKI258

Study type

Interventional

Funder types

Industry

Identifiers

NCT01596647

2011-001489-16 (EudraCT Number)

CTKI258A2119

Details and patient eligibility

About

This is a multi-center, open-label, phase I study to assess the effects of dovitinib (TKI258) on the pharmacokinetics of a cocktail of caffeine, diclofenac, omeprazole and midazolam in patients with advanced solid tumors, excluding breast cancer. The aim of this study is to evaluate the potential effect of dovitinib (TKI258) on the metabolism of the probe drugs caffeine, diclofenac, omeprazole and midazolam, which are metabolized by CYP1A2, CYP2C9, CYP2C19 and CYP3A4 respectively (Cytochrome P450 isoenzyme), comparing the single-dose pharmacokinetics (AUCtlast, AUCinf and Cmax parameters) of each of the individual probe drug co-administered with and without multiple dose of dovitinib (TKI258) 500 mg under a 5 days on / 2 days off dose schedule. The study foresees two treatment phases: DDI (drug-drug interaction) followed by post-DDI. During the DDI phase patients receive treatment with the probe drug cocktail and dovitinib (TKI258). During the post-DDI phase patients may continue to receive treatment with dovitinib (TKI258) until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death or discontinuation from the study treatment for any other reason.

Enrollment

39 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients with a cytopathologically or histopathologically confirmed diagnosis of an advanced solid tumor, excluding breast cancer which has progressed despite standard therapy or for which no standard therapy exists
ECOG performance status 0 or 1 and anticipated life expectancy ≥ 3 months
Patient must meet protocol-specific laboratory values

Exclusion criteria

Patients with brain metastases
Patients who have received or who are expected to receive any prohibited medications and therapies
Patients who have received CYP1A2 inducer, CYP2C9/2C19 inducer or CYP3A4 inducer medications within 30 days prior to start study treatment or are expected to receive during the first 14 days after starting the study treatment
Patients with a known hypersensitivity to benzodiazepines
Patients who have not recovered from previous anti-cancer therapies
Patient with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of TKI258
Patients who have concurrent severe and/or uncontrolled concomitant medical conditions that could compromise participation in the study
Female patients who are pregnant or breast-feeding
Fertile males or women not willing to use highly effective methods of contraception
Other protocol-defined inclusion/exclusion criteria will apply