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A DDI Study to Assess the Effect of INC280 on the PK of Midazolam and Caffeine in Patients With cMET-dysregulated Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02520752
Recruitment Status : Completed
First Posted : August 13, 2015
Last Update Posted : June 14, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
Drg-drug Interaction (DDI) study to assess the effect of INC280 on the pharmacokinetics of midazolam and caffeine in patients with cMET-dysregulated advanced solid tumors

Condition or disease Intervention/treatment Phase
cMET-dysregulated Advanced Solid Tumors Drug: INC280 Drug: Midazolam Drug: Caffeine Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Multicenter, Open-label, Single-sequence Drug-drug Interaction Study to Assess the Effect of INC280 on the Pharmacokinetics of Midazolam and Caffeine in Patients With cMET-dysregulated Advanced Solid Tumors
Actual Study Start Date : December 10, 2015
Actual Primary Completion Date : January 30, 2017
Actual Study Completion Date : September 12, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Caffeine

Arm Intervention/treatment
Experimental: INC280 Drug: INC280
Drug: Midazolam
Drug: Caffeine



Primary Outcome Measures :
  1. AUClast of midazolam and caffeine [ Time Frame: Up to 72 hours post midazolam and caffeine dose ]
    midazolam and caffeine pharmacokinetic parameters

  2. AUCinf of midazolam and caffeine [ Time Frame: Up to 72 hours post midazolam and caffeine dose ]
    midazolam and caffeine pharmacokinetic parameter

  3. Lambda_z of midazolam and caffeine [ Time Frame: Up to 72 hours post midazolam and caffeine dose ]
    midazolam and caffeine pharmacokinetic parameter

  4. Cmax of midazolam and caffeine [ Time Frame: Up to 72 hours post midazolam and caffeine dose ]
    midazolam and caffeine pharmacokinetic parameter

  5. Tmax of midazolam and caffeine [ Time Frame: Up to 72 hours post midazolam and caffeine dose ]
    midazolam and caffeine pharmacokinetic parameter

  6. T1/2 of midazolam and caffeine [ Time Frame: Up to 72 hours post midazolam and caffeine dose ]
    midazolam and caffeine pharmacokinetic parameter

  7. CL/F of midazolam and caffeine [ Time Frame: Up to 72 hours post midazolam and caffeine dose ]
    midazolam and caffeine pharmacokinetic parameter

  8. Vz/F of midazolam and caffeine [ Time Frame: Up to 72 hours post midazolam and caffeine dose ]
    midazolam and caffeine pharmacokinetic parameter


Secondary Outcome Measures :
  1. Adverse events based on the CTCAE v4.03 grade (severity) and other safety data (e.g.,ECG, vital signs, laboratory results) [ Time Frame: From consent to 30 days post last dose ]
    To assess safety and tolerability of INC280 in patients with cMET-dysregulated advanced solid tumors

  2. Overall response rate of patients treated with INC280 [ Time Frame: Baseline, every 6 weeks ]
    Overall response rate is defined as Complete Response and Partial Response calculated per RECIST 1.1, per investigator assessment

  3. Disease control rate of patients treated with INC280 [ Time Frame: Baseline, every 6 weeks ]
    Disease control rate is defined as calculated as the proportion of patients with best overall response of Complete Response, Partial Response, or Stable Disease calculated per RECIST 1.1, per investigator assessment



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients must have:

  • advanced solid tumors and have confirmed cMET dysregulation
  • at least one measurable lesion as defined by RECIST 1.1.
  • recovered from all toxicities related to prior anti-cancer therapies
  • adequate organ function
  • ECOG performance status (PS) of 0 or 1

Exclusion Criteria:

Patients must not have:

  • known hypersensitivity to any of the excipients of INC280 or to benzodiazepines or known intolerance and hypersensitivity to caffeine
  • symptomatic central nervous system (CNS) metastases who are neurologically unstable
  • presence or history of carcinomatous meningitis
  • history of another primary malignancy that is currently clinically significant or currently requires active intervention
  • Clinically significant, uncontrolled heart diseases, including QTcF ≥ 450 ms (male patients), ≥ 460 ms (female patients) on the screening ECG
  • Thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting INC280
  • Major surgery within 4 weeks prior to starting INC280
  • Patients receiving unstable or increasing doses of corticosteroids.
  • Impairment of GI function or GI disease that may significantly alter the absorption of INC280
  • Patients who have received or consumed, or are expected to receive or consume midazolam or caffeine-containing products (e.g., tea, coffee, cola), within 2 days prior to Day 1 and during the whole duration of the DDI phase (i.e., from Day -2 to Day 12)

Other protocol-defined inclusion/exclusion criteria may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02520752


Locations
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United States, Georgia
Emory University School of Medicine/Winship Cancer Institute SC-2
Atlanta, Georgia, United States, 30322
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Bulgaria
Novartis Investigative Site
Sofia, Bulgaria, 1756
Denmark
Novartis Investigative Site
Copenhagen, Denmark, DK-2100
France
Novartis Investigative Site
Dijon Cedex, Cote D Or, France, 21034
Novartis Investigative Site
Pierre Benite, France, 69310
Italy
Novartis Investigative Site
Rozzano, MI, Italy, 20089
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08003
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Santiago de Compostela, Galicia, Spain, 15706
United Kingdom
Novartis Investigative Site
London, United Kingdom, W12 0HS
Novartis Investigative Site
Manchester, United Kingdom, M20 9BX
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02520752    
Other Study ID Numbers: CINC280A2103
First Posted: August 13, 2015    Key Record Dates
Last Update Posted: June 14, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
cMET, INC280, caffeine, midazolam
Additional relevant MeSH terms:
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Neoplasms
Midazolam
Caffeine
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Central Nervous System Stimulants
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents