A Drug-drug Interaction (DDI) Study to Assess the Effect of INC280 on the Pharmacokinetics of Digoxin and Rosuvastatin in Patients With cMET-dysregulated Advanced Solid Tumors

Study Overview
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Brief Summary
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the study aim to assess the effect of INC280 on the pharmacokinetics of digoxin and rosuvastatin 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 Digoxin and Rosuvastatin 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: digoxin
* Drug: rosuvastatin


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 prior treatment with cMET or HGF-targeting inhibitor known hypersensitivity to digoxin or rosuvastatin or its excipients 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 msec (male patients), ≥ 460 msec (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 are expected to receive digoxin or rosuvastatin within 21 days prior to the beginning of the DDI phase (Day 1) and for the duration of the DDI phase. 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: digoxin<br> <br> Drug: rosuvastatin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUClast of digoxin and rosuvastatin | digoxin and rosuvastatin pharmacokinetics parameters | Up to 240 hours post digoxin and rosuvastatin dose | 
| AUCinf of digoxin and rosuvastatin | digoxin and rosuvastatin pharmacokinetics parameters | Up to 240 hours post digoxin and rosuvastatin dose | 
| Lambda_z of digoxin and rosuvastatin | digoxin and rosuvastatin pharmacokinetics parameters | Up to 240 hours post digoxin and rosuvastatin dose | 
| Cmax of digoxin and rosuvastatin | digoxin and rosuvastatin pharmacokinetics parameters | Up to 240 hours post digoxin and rosuvastatin dose | 
| Tmax of digoxin and rosuvastatin | digoxin and rosuvastatin pharmacokinetics parameters | Up to 240 hours post digoxin and rosuvastatin dose | 
| T1/2 of digoxin and rosuvastatin | digoxin and rosuvastatin pharmacokinetics parameters | Up to 240 hours post digoxin and rosuvastatin dose | 
| CL/F of digoxin and rosuvastatin | digoxin and rosuvastatin pharmacokinetics parameters | Up to 240 hours post digoxin and rosuvastatin dose | 
| Vz/F of digoxin and rosuvastatin | digoxin and rosuvastatin pharmacokinetics parameters | Up to 240 hours post digoxin and rosuvastatin 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 from Day 1 until date of progression or death whichever comes first | Up to 12 months | 
| 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 from Day 1 until date of progression or death whichever comes first | Up to 12 months | 
| Concentration of INC280 during DDI phase | INC280 concentrations collected on Day 22 during DDI phase and Cycle 2 Day 1 during post DDI phase along with a listing of individual values. | Day 22, Cycle 2 Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cMET, INC280, rosuvastatin, digoxin