Completed

NCT Number: NCT01596647

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

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.

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Key information

Conditions

Advanced Solid Tumors, Excluding Breast Cancer Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

University of Kansas Cancer Center Medical Center, Kansas City, Kansas, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Caffeine

Drug

single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam

Other names: probe drug

Diclofenac

Drug

single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam

Other names: probe drug

Omeprazole

Drug

single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam

Other names: probe drug

midazolam

Drug

single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam

Other names: probe drug

TKI258

Drug

dovitinib, 5 days on / 2 days off dose schedule

Other names: dovitinib

Primary outcomes

Probe substrate pharmacokinetics (PK) parameters: Cmax (Maximum (peak) concentration of drug)

Time frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters: AUCtlast (Area Under the Curve)

Time frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters: AUCinf

Time frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters:Tmax (Time to maximum concentration)

Time frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters: HL (Half-life time)

Time frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters:CL/F (Apparent Oral Clearance)

Time frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters:Vz/F (apparent volume of distribution)

Time frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),

Secondary outcomes

Frequency and severity of AEs (Adverse Events)

Time frame: up to at least 30 days after the last dose of dovitinib (TKI258)
Preliminary evidence of antitumor activity of dovitinib (TKI258)

Time frame: every 8 weeks until progression of disease

overall response based on investigator's assessment and best overall response using RECIST 1.1
Frequency and severity of SAEs (Serious Adverse Events)

Time frame: up to at least 30 days after the last dose of dovitinib (TKI258)

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Phase I, Multi-center, Open-label, Drug-drug Interaction Study to Assess the Effect of TKI258 on the Pharmacokinetics of Caffeine, Diclofenac, Omeprazole and Midazolam Administered as a Four-drug Cocktail in Patients With Advanced Solid Tumors, Excluding Breast Cancer

Important dates

Study start: 2012
Primary completion: 2014
Study completion: 2014
First posted: May 11, 2012
Registry last updated: Dec 21, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed