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

Information source: Novartis
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Advanced Solid Tumors, Excluding Breast Cancer

Intervention: dovitinib (TKI258) (Drug); fluvoxamine (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Novartis Pharmaceuticals

Official(s) and/or principal investigator(s):
Novartis Pharmaceuticals, Study Director, Affiliation: Novartis Pharmaceuticals

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.

Clinical Details

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

Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

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

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

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

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

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

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

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

Secondary outcome:

Frequency and severity of AEs (Adverse Events)

Frequency and severity of SAEs (Serious Adverse Events)

Preliminary evidence of antitumor activity of dovitinib (TKI258)

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

Novartis Investigative Site, Copenhagen DK-2100, Denmark

Novartis Investigative Site, Amsterdam 1066 CX, Netherlands

Novartis Investigative Site, Chur 7000, Switzerland

Novartis Investigative Site, Genève 1211, Switzerland

Montefiore Medical Center Montefiore Medical Center (SC), Bronx, New York 10467, United States

Cancer Therapy & Research Center / UT Health Science Center SC, San Antonio, Texas 78229, United States

Additional Information

Starting date: May 2013
Last updated: November 4, 2014

Page last updated: August 23, 2015

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