Clinical trial NCT02520752: A DDI Study to Assess the Effect of INC280 on the PK of Midazolam and Caffeine 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 Midazolam and Caffeine 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, caffeine, midazolam
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-08-13
Enrollment: 37
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: 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


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 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/exclusion criteria may apply

Primary outcomes:
measure: AUClast of midazolam and caffeine
timeFrame: Up to 72 hours post midazolam and caffeine dose
measure: AUCinf of midazolam and caffeine
timeFrame: Up to 72 hours post midazolam and caffeine dose
measure: Lambda_z of midazolam and caffeine
timeFrame: Up to 72 hours post midazolam and caffeine dose
measure: Cmax of midazolam and caffeine
timeFrame: Up to 72 hours post midazolam and caffeine dose
measure: Tmax of midazolam and caffeine
timeFrame: Up to 72 hours post midazolam and caffeine dose
measure: T1/2 of midazolam and caffeine
timeFrame: Up to 72 hours post midazolam and caffeine dose
measure: CL/F of midazolam and caffeine
timeFrame: Up to 72 hours post midazolam and caffeine dose
measure: Vz/F of midazolam and caffeine
timeFrame: Up to 72 hours post midazolam and caffeine 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: Baseline, every 6 weeks
measure: Disease control rate of patients treated with INC280
timeFrame: Baseline, every 6 weeks
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University School of Medicine/Winship Cancer Institute SC-2
state: Georgia
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Copenhagen
country: Denmark
facility: Novartis Investigative Site
city: Dijon Cedex
country: France
facility: Novartis Investigative Site
state: Cote D Or
city: Pierre Benite
country: France
facility: Novartis Investigative Site
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
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: