Clinical trial NCT02468661: 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: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Keywords: 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)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-06-11
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination
timeFrame: First 28 days of dosing
Secondary outcomes:
measure: Phase Ib: Overall response rate (ORR)
timeFrame: Every 3 weeks, up to 5 years
measure: Phase Ib: Disease Control Rate (DCR)
timeFrame: Every 6 weeks, up to 2 years
measure: Phase Ib: Duration of Response (DOR)
timeFrame: Every 6 weeks, up to 2 years
measure: Phase Ib: Progression-free Survival (PFS)
timeFrame: Every 6 weeks, up to 2 years
measure: Phase Ib: Number of patients with adverse events (AEs) as a measure of safety and tolerability
timeFrame: Every 3 weeks, up to 2 years
measure: Phase Ib: Plasma concentration-time profiles of INC280 and pharmacokinetic parameters
timeFrame: 6 weeks
measure: Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Los Angeles Hematology/Oncology Medical Group
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center Chao Family SC
state: California
city: Detroit
country: United States
facility: Henry Ford Hospital SC
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center SC
state: New Hampshire
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Brussel
country: Belgium
facility: Novartis Investigative Site
city: Charleroi
country: Belgium
facility: Novartis Investigative Site
city: Nice Cedex 2
country: France
facility: Novartis Investigative Site
state: Alpes Maritimes
city: Bordeaux
country: France
facility: Novartis Investigative Site
city: Caen Cedex
country: France
facility: Novartis Investigative Site
city: Marseille cedex 05
country: France
facility: Novartis Investigative Site
city: Strasbourg Cedex
country: France
facility: Novartis Investigative Site
city: Tübingen
country: Germany
facility: Novartis Investigative Site
state: Baden-Wuerttemberg
city: Regensburg
country: Germany
facility: Novartis Investigative Site
state: Bavaria
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bergamo
country: Italy
facility: Novartis Investigative Site
state: BG
city: Brescia
country: Italy
facility: Novartis Investigative Site
state: BS
city: Meldola
country: Italy
facility: Novartis Investigative Site
state: FC
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Parma
country: Italy
facility: Novartis Investigative Site
state: PR
city: Verona
country: Italy
facility: Novartis Investigative Site
state: VR
city: Fukuoka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Akashi
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Sendai city
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Okayama-city
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: NKI-AVL, Department of Thoracic-Oncology
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: