Pharmacokinetic Drug-drug Interaction Study of Dovitinib (TKI258) in Patients With Advanced Solid Tumors. (CTKI258A2120)

This study is currently recruiting participants.
Verified November 2013 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01700270
First received: October 2, 2012
Last updated: November 6, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Advanced Solid Tumors, Excluding Breast Cancer
Drug: dovitinib (TKI258)
Drug: fluvoxamine
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Frequency and severity of AEs (Adverse Events) [ Time Frame: up to at least 30 days after the last dose of dovitinib (TKI258) ] [ Designated as safety issue: Yes ]
  • Frequency and severity of SAEs (Serious Adverse Events) [ Time Frame: up to at least 30 days after the last dose of dovitinib (TKI258) ] [ Designated as safety issue: Yes ]
  • Preliminary evidence of antitumor activity of dovitinib (TKI258) [ Time Frame: every 8 weeks until progression of disease ] [ Designated as safety issue: No ]
    overall response based on investigator assessment and best overall response using RECIST 1.1


Estimated Enrollment: 32
Study Start Date: May 2013
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: dovitinib (TKI258)
dovitinib, 5 days on / 2 days off dose schedule
Drug: dovitinib (TKI258) Drug: fluvoxamine
perpetrator drug; 7 days of dosing

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01700270

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

Locations
United States, Missouri
Washington University School Of Medicine-Siteman Cancer Ctr Wash Univ Withdrawn
St. Louis, Missouri, United States, 63110
United States, New York
Montefiore Medical Center Montefiore Medical Center (SC) Active, not recruiting
Bronx, New York, United States, 10467
United States, Texas
Cancer Therapy & Research Center / UT Health Science Center SC Terminated
San Antonio, Texas, United States, 78229
Denmark
Novartis Investigative Site Active, not recruiting
Copenhagen, Denmark, DK-2100
Netherlands
Novartis Investigative Site Recruiting
Amsterdam, Netherlands, 1066 CX
Switzerland
Novartis Investigative Site Active, not recruiting
Chur, Switzerland, 7000
Novartis Investigative Site Active, not recruiting
Genève, Switzerland, 1211
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01700270     History of Changes
Other Study ID Numbers: CTKI258A2120, 2012-001546-18
Study First Received: October 2, 2012
Last Updated: November 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Fluvoxamine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants

ClinicalTrials.gov processed this record on April 17, 2014