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

This study is currently recruiting participants.
Verified March 2013 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01596647
First received: March 23, 2012
Last updated: March 1, 2013
Last verified: March 2013
History of Changes
  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:

U.S. FDA Resources

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 ]

Estimated Enrollment: 40
Study Start Date: May 2012
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: July 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01596647

Contacts
Contact: Novartis Pharmaceuticals +1(800)340-6843

Locations
United States, Kansas
University of Kansas Cancer Center Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Roby Nicklow     913-945-7086     nickl004@umn.edu    
Principal Investigator: Kapil N. Bhalla            
United States, Michigan
Henry Ford Hospital Henry Ford Not yet recruiting
Detroit, Michigan, United States, 48202-2689
Contact: Tiffany Pearce     313-916-8862     tpearce1@hfhs.org    
Principal Investigator: Ding Wang            
United States, Minnesota
University of Minnesota Not yet recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Roby Nicklow     612-624-9452     nickl004@umn.edu    
Principal Investigator: Arkadiusz Z. Dudek            
United States, Nevada
Comprehensive Cancer Centers Not yet recruiting
Las Vegas, Nevada, United States, 89169
Contact: Ramirez Ana Arlene     702-952-3400     Ana.ramirez@usoncology.com    
Principal Investigator: Fadi Braiteh            
United States, New Jersey
Cancer Institute of New Jersey Dept of Cancer Institute of NJ Recruiting
New Brunswick, New Jersey, United States, 08901
Contact: Anna Wong     732-235-8663        
Principal Investigator: Rebecca Moss            
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: March 1, 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
Neoplasms by Site
Breast Diseases
Skin Diseases
Caffeine
Midazolam
Diclofenac
Omeprazole
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Phosphodiesterase Inhibitors
 Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Adjuvants, Anesthesia

ClinicalTrials.gov processed this record on May 19, 2013