cMET-dysregulated Advanced Solid Tumors
Conditions
Keywords
cMET, INC280, caffeine, midazolam
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
Interventions
DRUGINC280
DRUGMidazolam
DRUGCaffeine
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vz/F of midazolam and caffeine | Up to 72 hours post midazolam and caffeine dose | midazolam and caffeine pharmacokinetic parameter |
| Tmax of midazolam and caffeine | Up to 72 hours post midazolam and caffeine dose | midazolam and caffeine pharmacokinetic parameter |
| T1/2 of midazolam and caffeine | Up to 72 hours post midazolam and caffeine dose | midazolam and caffeine pharmacokinetic parameter |
| CL/F of midazolam and caffeine | Up to 72 hours post midazolam and caffeine dose | midazolam and caffeine pharmacokinetic parameter |
| AUClast of midazolam and caffeine | Up to 72 hours post midazolam and caffeine dose | midazolam and caffeine pharmacokinetic parameters |
| AUCinf of midazolam and caffeine | Up to 72 hours post midazolam and caffeine dose | midazolam and caffeine pharmacokinetic parameter |
| Lambda_z of midazolam and caffeine | Up to 72 hours post midazolam and caffeine dose | midazolam and caffeine pharmacokinetic parameter |
| Cmax of midazolam and caffeine | Up to 72 hours post midazolam and caffeine dose | midazolam and caffeine pharmacokinetic parameter |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate of patients treated with INC280 | Baseline, every 6 weeks | Overall response rate is defined as Complete Response and Partial Response calculated per RECIST 1.1, per investigator assessment |
| Disease control rate of patients treated with INC280 | 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 |
| Adverse events based on the CTCAE v4.03 grade (severity) and other safety data (e.g.,ECG, vital signs, laboratory results) | From consent to 30 days post last dose | To assess safety and tolerability of INC280 in patients with cMET-dysregulated advanced solid tumors |
Countries
Bulgaria, Denmark, France, Italy, Spain, United Kingdom, United States
Outcome results
None listed