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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01596647
First received: March 23, 2012
Last updated: October 18, 2013
Last verified: October 2013
  Purpose

This is a multi-center, open-label, phase I study to assess the effects of dovitinib (TKI258) on the pharmacokinetics of a cocktail of caffeine, diclofenac, omeprazole and midazolam in patients with advanced solid tumors, excluding breast cancer. The aim of this study is to evaluate the potential effect of dovitinib (TKI258) on the metabolism of the probe drugs caffeine, diclofenac, omeprazole and midazolam, which are metabolized by CYP1A2, CYP2C9, CYP2C19 and CYP3A4 respectively (Cytochrome P450 isoenzyme), comparing the single-dose pharmacokinetics (AUCtlast, AUCinf and Cmax parameters) of each of the individual probe drug co-administered with and without multiple dose of dovitinib (TKI258) 500 mg under a 5 days on / 2 days off dose schedule. The study foresees two treatment phases: DDI (drug-drug interaction) followed by post-DDI. During the DDI phase patients receive treatment with the probe drug cocktail and dovitinib (TKI258). During the post-DDI phase patients may continue to receive treatment with dovitinib (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: caffeine
Drug: diclofenac
Drug: omeprazole
Drug: midazolam
Drug: TKI258
Phase 1

Study Type: Interventional
Study Design: 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 TKI258 on the Pharmacokinetics of Caffeine, Diclofenac, Omeprazole and Midazolam Administered as a Four-drug Cocktail in Patients With Advanced Solid Tumors, Excluding Breast Cancer

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Probe substrate pharmacokinetics (PK) parameters: Cmax (Maximum (peak) concentration of drug) [ Time Frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase), ] [ Designated as safety issue: No ]
  • Probe substrate PK parameters: AUCtlast (Area Under the Curve) [ Time Frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase), ] [ Designated as safety issue: No ]
  • Probe substrate PK parameters: AUCinf [ Time Frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase), ] [ Designated as safety issue: No ]
  • Probe substrate PK parameters:Tmax (Time to maximum concentration) [ Time Frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase), ] [ Designated as safety issue: No ]
  • Probe substrate PK parameters: HL (Half-life time) [ Time Frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase), ] [ Designated as safety issue: No ]
  • Probe substrate PK parameters:CL/F (Apparent Oral Clearance) [ Time Frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase), ] [ Designated as safety issue: No ]
  • Probe substrate PK parameters:Vz/F (apparent volume of distribution) [ Time Frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI 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 ]
  • 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's assessment and best overall response using RECIST 1.1

  • 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 ]

Enrollment: 38
Study Start Date: May 2012
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TKI258 (dovitinib)
dovitinib, 5 days on / 2 days off dose schedule
Drug: caffeine
single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam
Other Name: probe drug
Drug: diclofenac
single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam
Other Name: probe drug
Drug: omeprazole
single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam
Other Name: probe drug
Drug: midazolam
single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam
Other Name: probe drug
Drug: TKI258
dovitinib, 5 days on / 2 days off dose schedule
Other Name: dovitinib

  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 anticipated life expectancy ≥ 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 inducer, CYP2C9/2C19 inducer or CYP3A4 inducer medications within 30 days prior to start study treatment or are expected to receive during the first 14 days after starting the study treatment
  • Patients with a known hypersensitivity to benzodiazepines
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01596647

Locations
United States, Kansas
University of Kansas Cancer Center Medical Center
Kansas City, Kansas, United States, 66160
United States, Michigan
Henry Ford Hospital Henry Ford
Detroit, Michigan, United States, 48202-2689
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Nevada
Comprehensive Cancer Centers
Las Vegas, Nevada, United States, 89169
United States, New Jersey
Cancer Institute of New Jersey Dept of Cancer Institute of NJ
New Brunswick, New Jersey, United States, 08901
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: NCT01596647     History of Changes
Other Study ID Numbers: CTKI258A2119, 2011-001489-16
Study First Received: March 23, 2012
Last Updated: October 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
cancer, tumors, phase I, drug-drug interaction, pharmacokinetic, probe drug, caffeine, diclofenac, omeprazole, midazolam, CYP1A2, CYP2C9, CYP2C19, CYP3A4

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Caffeine
Diclofenac
Midazolam
Omeprazole
Adjuvants, Anesthesia
Analgesics
Analgesics, Non-Narcotic
Anesthetics
Anesthetics, General
Anesthetics, Intravenous
Anti-Anxiety Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Anti-Ulcer Agents
Antirheumatic Agents
Central Nervous System Agents
Central Nervous System Depressants
Central Nervous System Stimulants
Cyclooxygenase Inhibitors
Enzyme Inhibitors
GABA Agents
GABA Modulators
Gastrointestinal Agents
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 23, 2014