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
- Conditions
- cMET-dysregulated Advanced Solid Tumors
- Interventions
- Registration Number
- NCT02626234
- Lead Sponsor
- Novartis Pharmaceuticals
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description INC280 rosuvastatin - INC280 digoxin - INC280 INC280 -
- Primary Outcome Measures
Name Time Method Tmax 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
Cmax 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
AUClast 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
Lambda_z of digoxin and rosuvastatin Up to 240 hours post digoxin and rosuvastatin dose digoxin and rosuvastatin pharmacokinetics parameters
- Secondary Outcome Measures
Name Time Method 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
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
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
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.
Trial Locations
- Locations (3)
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Novartis Investigative Site
🇬🇧Manchester, United Kingdom
Emory University School of Medicine/Winship Cancer Institute Phase 1 Working Group
🇺🇸Atlanta, Georgia, United States