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

Advanced Solid Tumors, Excluding Breast Cancer Clinical Trial

— CTKI258A2120  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01700270
• Other study ID #: CTKI258A2120
• Secondary ID: 2012-001546-18
• Status: Completed
• Phase: Phase 1
• Start date: May 2013
• Est. completion date: August 2014

Study information

• Verified date: November 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors, Excluding Breast Cancer
• Neoplasms

Intervention

Drug:
• dovitinib (TKI258)

• fluvoxamine
perpetrator drug; 7 days of dosing

Locations

Country	Name	City	State
Denmark	Novartis Investigative Site	Copenhagen
Netherlands	Novartis Investigative Site	Amsterdam
Switzerland	Novartis Investigative Site	Chur
Switzerland	Novartis Investigative Site	Genève
United States	Montefiore Medical Center Montefiore Medical Center (SC)	Bronx	New York
United States	Cancer Therapy & Research Center / UT Health Science Center SC	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Denmark,  Netherlands,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TKI258 pharmacokinetics (PK) parameters: Cmax (Maximum (peak) concentration of drug)		multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
Primary	TKI258 pharmacokinetics (PK) parameters: AUC 0-24 hr (Area Under the Curve)		multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
Primary	TKI258 pharmacokinetics (PK) parameters: AUC 0-72 hr		multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
Primary	TKI258 pharmacokinetics (PK) parameters: Tmax (Time to maximum concentration)		multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
Primary	TKI258 pharmacokinetics (PK) parameters: T1/2 (Half-life time)		multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
Primary	TKI258 pharmacokinetics (PK) parameters: CL/F (Apparent Oral Clearance)		multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
Primary	TKI258 pharmacokinetics (PK) parameters: Vz/F (apparent volume of distribution)		multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
Secondary	Frequency and severity of AEs (Adverse Events)		up to at least 30 days after the last dose of dovitinib (TKI258)
Secondary	Frequency and severity of SAEs (Serious Adverse Events)		up to at least 30 days after the last dose of dovitinib (TKI258)
Secondary	Preliminary evidence of antitumor activity of dovitinib (TKI258)	overall response based on investigator assessment and best overall response using RECIST 1.1	every 8 weeks until progression of disease

External Links

•   Results for CTKI258A2120 on the Novartis Clinical Trial Website