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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

This study is currently recruiting participants.
Verified October 2017 by Novartis ( Novartis Pharmaceuticals )
Sponsor:
ClinicalTrials.gov Identifier:
NCT02468661
First Posted: June 11, 2015
Last Update Posted: October 16, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
  Purpose
The purpose of this study is 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 Intervention Phase
Non-Small Cell Lung Cancer Drug: INC280 single agent Drug: INC280 in combination with erlotinib Drug: Platinum/pemetrexed Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
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)

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination [ Time Frame: First 28 days of dosing ]
  • Phase II: Progression-free Survival (PFS) [ Time Frame: Every 6 weeks, up to 2 years ]
    Proportion of patients progression-free by investigator assessment per RECIST v1.1.


Secondary Outcome Measures:
  • Phase Ib: Overall Response Rate (ORR) [ Time Frame: Every 6 weeks, up to 2 years ]
    ORR, proportion of patients with a best overall response of complete response or partial response (CR+PR)

  • Phase Ib: Overall Survival (OS) [ Time Frame: Every 3 weeks, up to 5 years ]
    OS, defined as time from the first dose of study treatment to death due to any cause

  • 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).

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

  • 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.

  • Phase II: Overall Response Rate (ORR) by investigator's assessment according to RECIST v1.1 [ Time Frame: Every 6 weeks, up to 2 years ]
    ORR, proportion of patients with a best overall response of complete response or partial response (CR+PR)

  • Phase II: Overall Survival (OS) [ Time Frame: Every 3 weeks, up to 5 years ]
    OS, defined as time from randomization to death due to any cause

  • Phase II: Number of patients with AEs/serious adverse events (SAEs) as a measure of safety and tolerability (INC280 + erlotinib) [ Time Frame: Every 3 weeks, up to 2 years ]
    Safety and tolerability of the combination of INC280 and erlotinib assesed by change in vital signs, laboratory results and ECG.

  • Phase II: Number of patients with AEs/SAEs as a measure of safety and tolerability (INC280 alone) [ Time Frame: Every 3 weeks, up to 2 years ]
    Safety and tolerability of INC280 single agent assesed by change in vital signs, laboratory results and ECG.

  • Phase II: Plasma concentration of INC280 (INC280 + erlotinib) [ Time Frame: 6 weeks ]
    Composite Pharmacokinetics (PK) of INC280 in the presence of erlotinib

  • Phase II: Phase II: Plasma concentration of INC280 (INC280 alone) [ Time Frame: 6 weeks ]
    Composite PK of INC280 single agent

  • Phase II: Plama concentrations of INC280 (erlotinib + INC280) [ Time Frame: 6 weeks ]
    Composite PK of erlotinib in the presence of INC280.

  • 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

  • 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

  • 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

  • Phase II: Disease Control Rate (DCR) by investigator's assessment according to RECIST v1.1 [ Time Frame: Every 6 weeks, up to 2 years ]
    DCR, proportion of patients with best overall response of CR, PR or SD

  • Phase II: Duration of Response (DOR) by investigator's assessment according to RECIST v1.1 [ 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

  • Phase Ib: Number of patients with serious adverse events 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).

  • Phase II: Overall Response Rate (ORR), Disease Control Rate by investigator's assessment according to RECIST v1.1 [ Time Frame: Every 6 weeks, up to 2 years ]
    ORR, proportion of patients with a best overall response of complete response or partial response (CR+PR)


Estimated Enrollment: 135
Actual Study Start Date: September 23, 2015
Estimated Study Completion Date: March 31, 2020
Estimated Primary Completion Date: March 31, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: INC280 single agent Drug: INC280 single agent
Experimental: INC280 in combination with erlotinib Drug: INC280 in combination with erlotinib
Active Comparator: Platinum in combination with pemetrexed
Platinum (cisplatin or carboplatin) in combination with pemetrexed
Drug: Platinum/pemetrexed

  Eligibility

Information from the National Library of Medicine

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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 génération)
  • 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
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


Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com

  Show 40 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02468661     History of Changes
Other Study ID Numbers: CINC280B2201
First Submitted: June 1, 2015
First Posted: June 11, 2015
Last Update Posted: October 16, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Bronchial Neoplasms
Erlotinib Hydrochloride
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Pemetrexed
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors