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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

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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 )

Tracking Information
First Submitted Date  ICMJE June 1, 2015
First Posted Date  ICMJE June 11, 2015
Last Update Posted Date February 24, 2020
Actual Study Start Date  ICMJE September 23, 2015
Actual Primary Completion Date November 15, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 10, 2019)
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
Original Primary Outcome Measures  ICMJE
 (submitted: June 8, 2015)
  • 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 10, 2019)
  • 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)
  • 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 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 8, 2015)
  • 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)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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)
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: INC280 single agent
  • Drug: erlotinib
Study Arms  ICMJE
  • 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)
    Interventions:
    • 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)
    Interventions:
    • Drug: INC280 single agent
    • Drug: erlotinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 1, 2019)
23
Original Estimated Enrollment  ICMJE
 (submitted: June 8, 2015)
135
Actual Study Completion Date  ICMJE December 5, 2018
Actual Primary Completion Date November 15, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Singapore,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02468661
Other Study ID Numbers  ICMJE CINC280B2201
2015-001241-84 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP