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

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

the study aim to assess the effect of INC280 on the pharmacokinetics of digoxin and rosuvastatin in patients with cMET-dysregulated advanced solid tumors

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, A-1090
    • Novartis Investigative Site
• Belgium
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Novartis Investigative Site
• Czechia
  • Brno, Czechia, 65653
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 18547
    • Novartis Investigative Site
  • GR
    • Ioannina, GR, Greece, 455 00
      • Novartis Investigative Site
• Italy
  • Bologna, Italy, 40138
    • Novartis Investigative Site
  • Napoli, Italy, 80131
    • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20141
      • Novartis Investigative Site
  • TO
    • Candiolo, TO, Italy, 10060
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Madrid, Spain, 28222
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • 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 Phase 1 Working Group
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center

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
• 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 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: rosuvastatin; Drug: INC280; Drug: digoxin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUClast of digoxin and rosuvastatin	digoxin and rosuvastatin pharmacokinetics parameters	Up to 240 hours post digoxin and rosuvastatin dose
AUCinf of digoxin and rosuvastatin	digoxin and rosuvastatin pharmacokinetics parameters	Up to 240 hours post digoxin and rosuvastatin dose
Lambda_z of digoxin and rosuvastatin	digoxin and rosuvastatin pharmacokinetics parameters	Up to 240 hours post digoxin and rosuvastatin dose
Cmax of digoxin and rosuvastatin	digoxin and rosuvastatin pharmacokinetics parameters	Up to 240 hours post digoxin and rosuvastatin dose
Tmax of digoxin and rosuvastatin	digoxin and rosuvastatin pharmacokinetics parameters	Up to 240 hours post digoxin and rosuvastatin dose
T1/2 of digoxin and rosuvastatin	digoxin and rosuvastatin pharmacokinetics parameters	Up to 240 hours post digoxin and rosuvastatin dose
CL/F of digoxin and rosuvastatin	digoxin and rosuvastatin pharmacokinetics parameters	Up to 240 hours post digoxin and rosuvastatin dose
Vz/F of digoxin and rosuvastatin	digoxin and rosuvastatin pharmacokinetics parameters	Up to 240 hours post digoxin and rosuvastatin 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 from Day 1 until date of progression or death whichever comes first	Up to 12 months
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 from Day 1 until date of progression or death whichever comes first	Up to 12 months
Concentration of INC280 during DDI phase	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.	Day 22, Cycle 2 Day 1

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CINC280A2105 can be found Novartis Clinical trials results website

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2015
• Primary Completion (Actual): February 28, 2017
• Study Completion (Actual): April 28, 2017

Study Registration Dates

• First Submitted: October 13, 2015
• First Submitted That Met QC Criteria: December 7, 2015
• First Posted (Estimate): December 10, 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, rosuvastatin, digoxin
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Antimetabolites; Protective Agents; Cardiotonic Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Digoxin; Rosuvastatin Calcium
• Other Study ID Numbers: CINC280A2105

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