Brief 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.
Brief Title
Pharmacokinetic Drug-drug Interaction Study of Dovitinib (TKI258) in Patients With Advanced Solid Tumors.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Advanced Solid Tumors, Excluding Breast Cancer
Eligibility Criteria
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
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
Inclusion Criteria
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
inclusion/
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
inclusion/
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01700270
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CTKI258A2120
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Measure
TKI258 pharmacokinetics (PK) parameters: Cmax (Maximum (peak) concentration of drug)
Outcome Time Frame
multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
Outcome Measure
TKI258 pharmacokinetics (PK) parameters: AUC 0-24 hr (Area Under the Curve)
Outcome Time Frame
multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
Outcome Measure
TKI258 pharmacokinetics (PK) parameters: AUC 0-72 hr
Outcome Time Frame
multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
Outcome Measure
TKI258 pharmacokinetics (PK) parameters: Tmax (Time to maximum concentration)
Outcome Time Frame
multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
Outcome Measure
TKI258 pharmacokinetics (PK) parameters: T1/2 (Half-life time)
Outcome Time Frame
multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
Outcome Measure
TKI258 pharmacokinetics (PK) parameters: CL/F (Apparent Oral Clearance)
Outcome Time Frame
multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
Outcome Measure
TKI258 pharmacokinetics (PK) parameters: Vz/F (apparent volume of distribution)
Outcome Time Frame
multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
Secondary Ids
Secondary Id
2012-001546-18
Secondary Outcomes
Outcome Time Frame
up to at least 30 days after the last dose of dovitinib (TKI258)
Outcome Measure
Frequency and severity of AEs (Adverse Events)
Outcome Time Frame
up to at least 30 days after the last dose of dovitinib (TKI258)
Outcome Measure
Frequency and severity of SAEs (Serious Adverse Events)
Outcome Description
overall response based on investigator assessment and best overall response using RECIST 1.1
Outcome Time Frame
every 8 weeks until progression of disease
Outcome Measure
Preliminary evidence of antitumor activity of dovitinib (TKI258)
See Also Links
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sanjay Goel
Investigator Email
sgoel@montefiore.org
Investigator Phone
718-405-8404