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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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cMET-dysregulated Advanced Solid Tumors

Intervention / Treatment
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* Drug: INC280
* Drug: Midazolam
* Drug: Caffeine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INC280<br> | Drug: INC280<br> <br> Drug: Midazolam<br> <br> Drug: Caffeine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUClast of midazolam and caffeine | midazolam and caffeine pharmacokinetic parameters | Up to 72 hours post midazolam and caffeine dose | 
| AUCinf of midazolam and caffeine | midazolam and caffeine pharmacokinetic parameter | Up to 72 hours post midazolam and caffeine dose | 
| Lambda_z of midazolam and caffeine | midazolam and caffeine pharmacokinetic parameter | Up to 72 hours post midazolam and caffeine dose | 
| Cmax of midazolam and caffeine | midazolam and caffeine pharmacokinetic parameter | Up to 72 hours post midazolam and caffeine dose | 
| Tmax of midazolam and caffeine | midazolam and caffeine pharmacokinetic parameter | Up to 72 hours post midazolam and caffeine dose | 
| T1/2 of midazolam and caffeine | midazolam and caffeine pharmacokinetic parameter | Up to 72 hours post midazolam and caffeine dose | 
| CL/F of midazolam and caffeine | midazolam and caffeine pharmacokinetic parameter | Up to 72 hours post midazolam and caffeine dose | 
| Vz/F of midazolam and caffeine | midazolam and caffeine pharmacokinetic parameter | Up to 72 hours post midazolam and caffeine dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events based on the CTCAE v4.03 grade (severity) and other safety data (e.g.,ECG, vital signs, laboratory results) | To assess safety and tolerability of INC280 in patients with cMET-dysregulated advanced solid tumors | From consent to 30 days post last dose | 
| Overall response rate of patients treated with INC280 | Overall response rate is defined as Complete Response and Partial Response calculated per RECIST 1.1, per investigator assessment | Baseline, every 6 weeks | 
| Disease control rate of patients treated with INC280 | 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 | Baseline, every 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cMET, INC280, caffeine, midazolam