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Completed

NCT Number: NCT01700270

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

This is a multi-center, open-label, single-sequence, crossover, drug-drug interaction (DDI) study to assess the effect of the CYP1A2 inhibitor, fluvoxamine, on the PK of dovitinib in patients with advanced solid tumors, excluding breast cancer. The purpose of this study is to evaluate the effect of a CYP1A2 inhibitor, 100 mg fluvoxamine, on the PK of dovitinib when administered at a dose of 300 mg on the dosing schedule, 5 days on/2 days off. The study will consist of 2 phases: a Pharmacokinetic (PK) phase and a clinical treatment phase. The DDI test will be conducted in the PK phase. The DDI test will assess the steady state PK profile of dovitinib when administered alone and in the presence of the CYP1A2 inhibitor, fluvoxamine (AUC 0-24h, AUC 0-72h and Cmax parameters). During the clinical treatment phase patients may continue to receive treatment with 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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site, Copenhagen, Denmark

Loading trial locations.

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 an anticipated life expectancy of ≥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 or CYP3A inhibitor medications within 5 days prior to start study treatment or are expected to receive during the first 28 days after starting the study treatment - Patients who have received CYP1A2 or CYP3A inducer medications within 30 days prior to start study treatment or are expected to receive during the first 28 days after starting the study treatment - Patients who are actively taking antidepressants, benzodiazepines, serotonergic drugs, and/or monoamine oxidase inhibitors (MAOIs) - 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

Dovitinib (TKI258)

Drug

Fluvoxamine

Drug

perpetrator drug; 7 days of dosing

Primary outcomes

  1. TKI258 pharmacokinetics (PK) parameters: Cmax (Maximum (peak) concentration of drug)

    Time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)

  2. TKI258 pharmacokinetics (PK) parameters: AUC 0-24 hr (Area Under the Curve)

    Time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)

  3. TKI258 pharmacokinetics (PK) parameters: AUC 0-72 hr

    Time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)

  4. TKI258 pharmacokinetics (PK) parameters: Tmax (Time to maximum concentration)

    Time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)

  5. TKI258 pharmacokinetics (PK) parameters: T1/2 (Half-life time)

    Time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)

  6. TKI258 pharmacokinetics (PK) parameters: CL/F (Apparent Oral Clearance)

    Time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)

  7. TKI258 pharmacokinetics (PK) parameters: Vz/F (apparent volume of distribution)

    Time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)

Secondary outcomes

  1. Frequency and severity of AEs (Adverse Events)

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

  2. Frequency and severity of SAEs (Serious Adverse Events)

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

  3. Preliminary evidence of antitumor activity of dovitinib (TKI258)

    Time frame: every 8 weeks until progression of disease

    overall response based on investigator assessment and best overall response using RECIST 1.1

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 the CYP1A2 Inhibitor, Fluvoxamine, on Dovitinib (TKI258) Pharmacokinetics in Patients With Advanced Solid Tumors

Acronym: CTKI258A2120

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Oct 4, 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.

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