NCT01700270

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started May 2013

Geographic Reach
4 countries

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 2, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 4, 2012

Completed
7 months until next milestone

Study Start

First participant enrolled

May 1, 2013

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2014

Completed
Last Updated

December 21, 2020

Status Verified

November 1, 2014

Enrollment Period

1.3 years

First QC Date

October 2, 2012

Last Update Submit

December 17, 2020

Conditions

Advanced Solid Tumors, Excluding Breast Cancer

Outcome Measures

Primary Outcomes (7)

  • 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)

  • 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)

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

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

  • 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)

  • 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)

  • 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)

  • 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 Outcomes (3)

  • Frequency and severity of AEs (Adverse Events)

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

  • Frequency and severity of SAEs (Serious Adverse Events)

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

  • Preliminary evidence of antitumor activity of dovitinib (TKI258)

    every 8 weeks until progression of disease

Study Arms (1)

dovitinib (TKI258)

EXPERIMENTAL

dovitinib, 5 days on / 2 days off dose schedule

Drug: dovitinib (TKI258)Drug: fluvoxamine

Interventions

dovitinib (TKI258)DRUG
dovitinib (TKI258)
fluvoxamineDRUG

perpetrator drug; 7 days of dosing

dovitinib (TKI258)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Montefiore Medical Center Montefiore Medical Center (SC)

The Bronx, New York, 10467, United States

Location

Cancer Therapy & Research Center / UT Health Science Center SC

San Antonio, Texas, 78229, United States

Location

Novartis Investigative Site

Copenhagen, DK-2100, Denmark

Location

Novartis Investigative Site

Amsterdam, 1066 CX, Netherlands

Location

Novartis Investigative Site

Chur, 7000, Switzerland

Location

Novartis Investigative Site

Geneva, 1211, Switzerland

Location

Related Publications (1)

  • de Weger VA, Goel S, von Moos R, Schellens JHM, Mach N, Tan E, Anand S, Scott JW, Lassen U. A drug-drug interaction study to assess the effect of the CYP1A2 inhibitor fluvoxamine on the pharmacokinetics of dovitinib (TKI258) in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2018 Jan;81(1):73-80. doi: 10.1007/s00280-017-3469-4. Epub 2017 Nov 3.

    PMID: 29101463DERIVED

Related Links

MeSH Terms

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-oneFluvoxamine

Intervention Hierarchy (Ancestors)

OximesHydroxylaminesAminesOrganic Chemicals

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 2, 2012

First Posted

October 4, 2012

Study Start

May 1, 2013

Primary Completion

August 1, 2014

Study Completion

August 1, 2014

Last Updated

December 21, 2020

Record last verified: 2014-11

Locations

US(2)NL(1)CH(2)DK(1)