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

NCT02520752 | Completed Phase 1 FDA Drug

• 1 other identifier: CINC280A2103
• Study Type: interventional
• Target: 37
• Locations: 7 countries
• Sites: 12

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

Conditions

cMET-dysregulated Advanced Solid Tumors

Keywords

cMET, INC280, caffeine, midazolam

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (3)

• 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

• Overall response rate of patients treated with INC280

  Baseline, every 6 weeks

• Disease control rate of patients treated with INC280

  Baseline, every 6 weeks

Study Arms (1)

INC280

EXPERIMENTAL

Drug: INC280; Drug: Midazolam; Drug: Caffeine

Interventions

INC280 DRUG

INC280

Midazolam DRUG

INC280

Caffeine DRUG

INC280

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

Emory University School of Medicine/Winship Cancer Institute SC-2

Atlanta, Georgia, 30322, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Novartis Investigative Site

Sofia, 1756, Bulgaria

Location

Novartis Investigative Site

Copenhagen, DK-2100, Denmark

Location

Novartis Investigative Site

Dijon, Cote D Or, 21034, France

Location

Novartis Investigative Site

Pierre-Bénite, 69310, France

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Barcelona, Catalonia, 08003, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Santiago de Compostela, Galicia, 15706, Spain

Location

Novartis Investigative Site

London, W12 0HS, United Kingdom

Location

Novartis Investigative Site

Manchester, M20 9BX, United Kingdom

Location

Related Links

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

MeSH Terms

Interventions

capmatinib; Midazolam; Caffeine

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Xanthines; Alkaloids; Purinones; Purines

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2015
• First Posted: August 13, 2015
• Study Start: December 10, 2015
• Primary Completion: January 30, 2017
• Study Completion: September 12, 2017
• Last Updated: December 10, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); BU (1); US (2); FR (2); DK (1); IT (1); ES (3)