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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Notify MeKey information
Age range
18 year and older
Sex eligibility
All sexes
Study type
Interventional
Phase
Phase 1
Primary location
Novartis Investigative Site, Copenhagen, Denmark
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
Fluvoxamine
Drugperpetrator drug; 7 days of dosing
Primary outcomes
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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)
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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)
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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)
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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)
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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)
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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)
-
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
-
Frequency and severity of AEs (Adverse Events)
Time frame: up to at least 30 days after the last dose of dovitinib (TKI258)
-
Frequency and severity of SAEs (Serious 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 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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