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

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

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

Study Overview

• Status: Completed
• Conditions: cMET-dysregulated Advanced Solid Tumors
• Intervention / Treatment: Drug: Midazolam; Drug: Caffeine; Drug: INC280

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1756
    • Novartis Investigative Site
• Denmark
  • Copenhagen, Denmark, DK-2100
    • Novartis Investigative Site
• France
  • Pierre Benite, France, 69310
    • Novartis Investigative Site
  • Cote D Or
    • Dijon Cedex, Cote D Or, France, 21034
      • Novartis Investigative Site
• Italy
  • MI
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
• Spain
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08003
      • Novartis Investigative Site
  • Galicia
    • Santiago de Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, W12 0HS
    • Novartis Investigative Site
  • Manchester, United Kingdom, M20 9BX
    • Novartis Investigative Site
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine/Winship Cancer Institute SC-2
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: INC280	Drug: Midazolam; Drug: Caffeine; Drug: INC280

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUClast of midazolam and caffeine	midazolam and caffeine pharmacokinetic parameters	Up to 72 hours post midazolam and caffeine dose
AUCinf of midazolam and caffeine	midazolam and caffeine pharmacokinetic parameter	Up to 72 hours post midazolam and caffeine dose
Lambda_z of midazolam and caffeine	midazolam and caffeine pharmacokinetic parameter	Up to 72 hours post midazolam and caffeine dose
Cmax of midazolam and caffeine	midazolam and caffeine pharmacokinetic parameter	Up to 72 hours post midazolam and caffeine dose
Tmax of midazolam and caffeine	midazolam and caffeine pharmacokinetic parameter	Up to 72 hours post midazolam and caffeine dose
T1/2 of midazolam and caffeine	midazolam and caffeine pharmacokinetic parameter	Up to 72 hours post midazolam and caffeine dose
CL/F of midazolam and caffeine	midazolam and caffeine pharmacokinetic parameter	Up to 72 hours post midazolam and caffeine dose
Vz/F of midazolam and caffeine	midazolam and caffeine pharmacokinetic parameter	Up to 72 hours post midazolam and caffeine dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events based on the CTCAE v4.03 grade (severity) and other safety data (e.g.,ECG, vital signs, laboratory results)	To assess safety and tolerability of INC280 in patients with cMET-dysregulated advanced solid tumors	From consent to 30 days post last dose
Overall response rate of patients treated with INC280	Overall response rate is defined as Complete Response and Partial Response calculated per RECIST 1.1, per investigator assessment	Baseline, every 6 weeks
Disease control rate of patients treated with INC280	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	Baseline, every 6 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CINC280A2103 can be found on the Novartis Clinical trial results website

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2015
• Primary Completion (Actual): January 30, 2017
• Study Completion (Actual): September 12, 2017

Study Registration Dates

• First Submitted: August 9, 2015
• First Submitted That Met QC Criteria: August 11, 2015
• First Posted (Estimate): August 13, 2015

Study Record Updates

• Last Update Posted (Actual): December 10, 2020
• Last Update Submitted That Met QC Criteria: December 8, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: cMET, INC280, caffeine, midazolam
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Purinergic Antagonists; Purinergic Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Midazolam; Caffeine
• Other Study ID Numbers: CINC280A2103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No