A DDI Study to Assess the Effect of INC280 on the PK of Midazolam and Caffeine in Patients With cMET-dysregulated Advanced Solid Tumors

Phase 1

Completed

• Conditions: cMET-dysregulated Advanced Solid Tumors
• Interventions: Drug: INC280; Drug: Midazolam; Drug: Caffeine

• Registration Number: NCT02520752
• Lead Sponsor: Novartis Pharmaceuticals

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-08-09
• Study First Submitted QC: 2015-08-11
• Study First Posted: 2015-08-13
• Study Start: 2015-12-10
• Primary Completion: 2017-01-30
• Study Completion: 2017-09-12
• Status Verified: 2020-07
• Last Update Submitted: 2020-12-08
• Last Update Posted: 2020-12-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
INC280	INC280	-
INC280	Midazolam	-
INC280	Caffeine	-

Primary Outcome Measures

Name	Time	Method
Lambda_z 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
Vz/F of midazolam and caffeine	Up to 72 hours post midazolam and caffeine dose	midazolam and caffeine pharmacokinetic parameter
AUCinf 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
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

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
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

Trial Locations

Locations (3)

Novartis Investigative Site; 🇬🇧 Manchester, United Kingdom

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Emory University School of Medicine/Winship Cancer Institute SC-2; 🇺🇸 Atlanta, Georgia, United States