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A Safety and Efficacy Study of INC280 Alone, and in Combination With Erlotinib, Compared to Chemotherapy, in Advanced/Metastatic Non-small Cell Lung Cancer Patients With EGFR Mutation and cMET Amplification

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02468661
Recruitment Status : Terminated (Major challenge for enrollment of participants.)
First Posted : June 11, 2015
Last Update Posted : February 24, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief Summary:
The purpose of this study was to determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of INC280 in combination with erlotinib in the Phase Ib of this study, and to assess the anti-tumor activity and safety of INC280 alone, and in combination with erlotinib, versus platinum with pemetrexed in the Phase II of this study, in adult patients with EGFR mutated, cMET amplified, advanced/metastatic non-small cell lung cancer with acquired resistance to prior EGFR TKI.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: INC280 single agent Drug: erlotinib Phase 1

Detailed Description:

The decision was taken to halt study enrollment with Cohort #3 in Phase Ib. Therefore, activities for the planned Phase II were not initiated.

This decision to stop further development of this combination was taken due to the challenge for enrollment in this very rare patient population along with the rapidly evolving disease landscape setting.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The study started as a single assignment study which was to move to a parallel design (3 arms) but the study was stopped after cohort #3 in the phase I part and so never moved into phase 2.
Masking: None (Open Label)
Masking Description: The study started as a non-randomized study, and was to move into randomized part in phase II. However the study was stopped after cohort #3 in the phase I part and so never moved into phase II.
Primary Purpose: Treatment
Official Title: A Phase Ib/II, Open-label, Multicenter Trial With Oral cMET Inhibitor INC280 Alone and in Combination With Erlotinib Versus Platinum With Pemetrexed in Adult Patients With EGFR Mutated, cMET-amplified, Locally Advanced/Metastatic Non-small Cell Lung Cancer (NSCLC) With Acquired Resistance to Prior EGFR Tyrosine Kinase Inhibitor (EGFR TKI)
Actual Study Start Date : September 23, 2015
Actual Primary Completion Date : November 15, 2017
Actual Study Completion Date : December 5, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: INC280 200mg BID + ERL 150mg QD
Subjects who took INC280 200mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD)
 Drug: INC280 single agent
Drug: erlotinib
Experimental: INC280 400mg BID + ERL 150mg QD
Subjects who took INC280 400mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD)
 Drug: INC280 single agent
Drug: erlotinib


Outcome Measures
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Primary Outcome Measures :
  1. Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination [ Time Frame: First 28 days of dosing ]
    To determine MTD and/or RP2D of INC280 in combination with erlotinib


Secondary Outcome Measures :
  1. Phase Ib: Overall response rate (ORR) [ Time Frame: Every 3 weeks, up to 5 years ]
    ORR, proportion of patients with a best overall response of complete response or partial Response (CR+PR)

  2. Phase Ib: Disease Control Rate (DCR) [ Time Frame: Every 6 weeks, up to 2 years ]
    DCR, proportion of patients with best overall response of CR, PR or SD

  3. Phase Ib: Duration of Response (DOR) [ Time Frame: Every 6 weeks, up to 2 years ]
    DOR, defined as time from the first documented CR or PR to first documented progression or death due to any cause

  4. Phase Ib: Progression-free Survival (PFS) [ Time Frame: Every 6 weeks, up to 2 years ]
    PFS, defined as time from the first dose of study treatment to disease progression or death due to any cause

  5. Phase Ib: Number of patients with adverse events (AEs) as a measure of safety and tolerability [ Time Frame: Every 3 weeks, up to 2 years ]
    Safety and tolerability of INC280 in combination with erlotinib assessed by change in vital signs, laboratory results and electrocardiogram (ECG).

  6. Phase Ib: Plasma concentration-time profiles of INC280 and pharmacokinetic parameters [ Time Frame: 6 weeks ]
    Composite pharmacokinetics of INC280 in the presence of erlotinib.

  7. Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280 [ Time Frame: 6 weeks ]
    Composite pharmacokinetics of erlotinib in the presence of INC280.


Eligibility Criteria
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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Locally advanced or metastatic NSCLC
  • EGFR mutation (L858R and /or ex19del)
  • cMET amplification by FISH (GCN ≥ 6),
  • Acquired resistance to EGFR TKI (1st or 2nd generation)
  • ECOG performance status (PS) ≤ 1.

Exclusion Criteria:

  • Prior treatment with 3rd generation TKI

  • PhaseII : Prior treatment with any of the following agents:

    • Crizotinib, or any other cMET inhibitor or HGF-targeting inhibitor.
    • Concomitant EGFR TKI and platinum based chemotherapy as first line regimen.
    • Platinum-based chemotherapy as first line treatment
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02468661


Locations
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United States, California
Los Angeles Hematology/Oncology Medical Group
Los Angeles, California, United States, 90017
University of California Irvine Medical Center Chao Family SC
Orange, California, United States, 92868
United States, Michigan
Henry Ford Hospital SC
Detroit, Michigan, United States, 48202-2689
United States, New Hampshire
Dartmouth Hitchcock Medical Center SC
Lebanon, New Hampshire, United States, 03756
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98105
Belgium
Novartis Investigative Site
Brussel, Belgium, 1090
Novartis Investigative Site
Charleroi, Belgium, 6000
France
Novartis Investigative Site
Nice Cedex 2, Alpes Maritimes, France, 06189
Novartis Investigative Site
Bordeaux, France, 33076
Novartis Investigative Site
Caen Cedex, France, 14021
Novartis Investigative Site
Marseille cedex 05, France, 13385
Novartis Investigative Site
Strasbourg Cedex, France, 67091
Germany
Novartis Investigative Site
Tübingen, Baden-Wuerttemberg, Germany, 72076
Novartis Investigative Site
Regensburg, Bavaria, Germany, 93053
Novartis Investigative Site
Berlin, Germany, 13125
Italy
Novartis Investigative Site
Bergamo, BG, Italy, 24127
Novartis Investigative Site
Brescia, BS, Italy, 25123
Novartis Investigative Site
Meldola, FC, Italy, 47014
Novartis Investigative Site
Rozzano, MI, Italy, 20089
Novartis Investigative Site
Parma, PR, Italy, 43100
Novartis Investigative Site
Verona, VR, Italy, 37126
Japan
Novartis Investigative Site
Fukuoka-city, Fukuoka, Japan, 811-1395
Novartis Investigative Site
Akashi, Hyogo, Japan, 673-8558
Novartis Investigative Site
Sendai city, Miyagi, Japan, 980 0873
Novartis Investigative Site
Okayama-city, Okayama, Japan, 700-8558
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 05505
Novartis Investigative Site
Seoul, Korea, Republic of, 03080
Netherlands
NKI-AVL, Department of Thoracic-Oncology
Amsterdam, Netherlands, 1066 CX
Singapore
Novartis Investigative Site
Singapore, Singapore, 169610
Spain
Novartis Investigative Site
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site
Madrid, Spain, 28046
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02468661    
Other Study ID Numbers: CINC280B2201
2015-001241-84 ( EudraCT Number )
First Posted: June 11, 2015    Key Record Dates
Last Update Posted: February 24, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Non-Small Cell Lung Cancer
NSCLC
INC280
erlotinib
 advanced/metastatic non-small cell lung cancer
EGFR mutation
cMET amplification
EGFR tyrosine kinase inhibitor (EGFR TKI)
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
 Carcinoma, Bronchogenic
Bronchial Neoplasms
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action