cMET-dysregulated Advanced Solid Tumors
Conditions
Keywords
cMET, INC280, rosuvastatin, digoxin
Brief summary
the study aim to assess the effect of INC280 on the pharmacokinetics of digoxin and rosuvastatin in patients with cMET-dysregulated advanced solid tumors
Interventions
DRUGINC280
DRUGdigoxin
DRUGrosuvastatin
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 * 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUClast of digoxin and rosuvastatin | Up to 240 hours post digoxin and rosuvastatin dose | digoxin and rosuvastatin pharmacokinetics parameters |
| AUCinf of digoxin and rosuvastatin | Up to 240 hours post digoxin and rosuvastatin dose | digoxin and rosuvastatin pharmacokinetics parameters |
| Lambda_z of digoxin and rosuvastatin | Up to 240 hours post digoxin and rosuvastatin dose | digoxin and rosuvastatin pharmacokinetics parameters |
| Cmax of digoxin and rosuvastatin | Up to 240 hours post digoxin and rosuvastatin dose | digoxin and rosuvastatin pharmacokinetics parameters |
| Tmax of digoxin and rosuvastatin | Up to 240 hours post digoxin and rosuvastatin dose | digoxin and rosuvastatin pharmacokinetics parameters |
| T1/2 of digoxin and rosuvastatin | Up to 240 hours post digoxin and rosuvastatin dose | digoxin and rosuvastatin pharmacokinetics parameters |
| CL/F of digoxin and rosuvastatin | Up to 240 hours post digoxin and rosuvastatin dose | digoxin and rosuvastatin pharmacokinetics parameters |
| Vz/F of digoxin and rosuvastatin | Up to 240 hours post digoxin and rosuvastatin dose | digoxin and rosuvastatin pharmacokinetics parameters |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Overall response rate of patients treated with INC280 | Up to 12 months | 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 |
| Disease control rate of patients treated with INC280 | Up to 12 months | 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 |
| Concentration of INC280 during DDI phase | Day 22, Cycle 2 Day 1 | 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. |
Countries
Austria, Belgium, Czechia, Greece, Italy, Spain, United Kingdom, United States
Outcome results
None listed