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

December 17, 2020 updated by: Novartis Pharmaceuticals

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
39

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center Medical Center
    • Michigan
      • Detroit, Michigan, United States, 48202-2689
        • Henry Ford Hospital Henry Ford
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Cancer Institute of New Jersey Dept of Cancer Institute of NJ

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: TKI258 (dovitinib)
dovitinib, 5 days on / 2 days off dose schedule
Drug: caffeine
single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam
Other Names:
  • probe drug
Drug: diclofenac
single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam
Other Names:
  • probe drug
Drug: omeprazole
single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam
Other Names:
  • probe drug
Drug: midazolam
single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam
Other Names:
  • probe drug
Drug: TKI258
dovitinib, 5 days on / 2 days off dose schedule
Other Names:
  • dovitinib

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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),
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),
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),
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),
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),
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),
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),
multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Frequency and severity of AEs (Adverse Events)
Time Frame: up to at least 30 days after the last dose of dovitinib (TKI258)
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
every 8 weeks until progression of disease
Frequency and severity of SAEs (Serious Adverse Events)
Time Frame: up to at least 30 days after the last dose of dovitinib (TKI258)
up to at least 30 days after the last dose of dovitinib (TKI258)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2012

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2014

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 23, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 10, 2012

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 11, 2012

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 21, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 17, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CTKI258A2119
  • 2011-001489-16 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Advanced Solid Tumors, Excluding Breast Cancer

Clinical Trials on caffeine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings