Clinical trial NCT02626234: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: cMET-dysregulated Advanced Solid Tumors
Keywords: cMET, INC280, rosuvastatin, digoxin
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-12-10
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: AUClast of digoxin and rosuvastatin
timeFrame: Up to 240 hours post digoxin and rosuvastatin dose
measure: AUCinf of digoxin and rosuvastatin
timeFrame: Up to 240 hours post digoxin and rosuvastatin dose
measure: Lambda_z of digoxin and rosuvastatin
timeFrame: Up to 240 hours post digoxin and rosuvastatin dose
measure: Cmax of digoxin and rosuvastatin
timeFrame: Up to 240 hours post digoxin and rosuvastatin dose
measure: Tmax of digoxin and rosuvastatin
timeFrame: Up to 240 hours post digoxin and rosuvastatin dose
measure: T1/2 of digoxin and rosuvastatin
timeFrame: Up to 240 hours post digoxin and rosuvastatin dose
measure: CL/F of digoxin and rosuvastatin
timeFrame: Up to 240 hours post digoxin and rosuvastatin dose
measure: Vz/F of digoxin and rosuvastatin
timeFrame: Up to 240 hours post digoxin and rosuvastatin dose
Secondary outcomes:
measure: Adverse events based on the CTCAE v4.03 grade (severity) and other safety data (e.g.,ECG, vital signs, laboratory results)
timeFrame: From consent to 30 days post last dose
measure: Overall response rate of patients treated with INC280
timeFrame: Up to 12 months
measure: Disease control rate of patients treated with INC280
timeFrame: Up to 12 months
measure: Concentration of INC280 during DDI phase
timeFrame: Day 22, Cycle 2 Day 1
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University School of Medicine/Winship Cancer Institute Phase 1 Working Group
state: Georgia
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Edegem
country: Belgium
facility: Novartis Investigative Site
state: Antwerpen
city: Brno
country: Czechia
facility: Novartis Investigative Site
city: Ioannina
country: Greece
facility: Novartis Investigative Site
state: GR
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Candiolo
country: Italy
facility: Novartis Investigative Site
state: TO
city: Bologna
country: Italy
facility: Novartis Investigative Site
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: