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

cMET-dysregulated Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02520752
• Other study ID #: CINC280A2103
• Status: Completed
• Phase: Phase 1
• Start date: December 10, 2015
• Est. completion date: September 12, 2017

Study information

• Verified date: July 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: September 12, 2017
• Est. primary completion date: January 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• cMET-dysregulated Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• INC280

• Midazolam

• Caffeine

Locations

Country	Name	City	State
Bulgaria	Novartis Investigative Site	Sofia
Denmark	Novartis Investigative Site	Copenhagen
France	Novartis Investigative Site	Dijon Cedex	Cote D Or
France	Novartis Investigative Site	Pierre Benite
Italy	Novartis Investigative Site	Rozzano	MI
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Manchester
United States	Emory University School of Medicine/Winship Cancer Institute SC-2	Atlanta	Georgia
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Bulgaria,  Denmark,  France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUClast of midazolam and caffeine	midazolam and caffeine pharmacokinetic parameters	Up to 72 hours post midazolam and caffeine dose
Primary	AUCinf of midazolam and caffeine	midazolam and caffeine pharmacokinetic parameter	Up to 72 hours post midazolam and caffeine dose
Primary	Lambda_z of midazolam and caffeine	midazolam and caffeine pharmacokinetic parameter	Up to 72 hours post midazolam and caffeine dose
Primary	Cmax of midazolam and caffeine	midazolam and caffeine pharmacokinetic parameter	Up to 72 hours post midazolam and caffeine dose
Primary	Tmax of midazolam and caffeine	midazolam and caffeine pharmacokinetic parameter	Up to 72 hours post midazolam and caffeine dose
Primary	T1/2 of midazolam and caffeine	midazolam and caffeine pharmacokinetic parameter	Up to 72 hours post midazolam and caffeine dose
Primary	CL/F of midazolam and caffeine	midazolam and caffeine pharmacokinetic parameter	Up to 72 hours post midazolam and caffeine dose
Primary	Vz/F of midazolam and caffeine	midazolam and caffeine pharmacokinetic parameter	Up to 72 hours post midazolam and caffeine dose
Secondary	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
Secondary	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
Secondary	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

External Links

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