Non-Small Cell Lung CancerPhase 1NCT02468661
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
A Phase 1 study testing INC280 single agent and erlotinib in people with Non-Small Cell Lung Cancer, run by Novartis Pharmaceuticals at 32 sites in 10 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- INC280 single agent and erlotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 32 sitesin 10 countries
- Study dates
- 23 Sep 2015to 5 Dec 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
32 sites in 10 countries.
32 sites in 10 countries
Italy6 sites
Novartis Investigative Site
Bergamo, BG, 24127
Novartis Investigative Site
Brescia, BS, 25123
Novartis Investigative Site
Meldola, FC, 47014
Novartis Investigative Site
Parma, PR, 43100
Novartis Investigative Site
Rozzano, MI, 20089
Novartis Investigative Site
Verona, VR, 37126
United States5 sites
Henry Ford Hospital SC
Detroit, Michigan, 48202-2689
Dartmouth Hitchcock Medical Center SC
Lebanon, New Hampshire, 03756
Los Angeles Hematology/Oncology Medical Group
Los Angeles, California, 90017
University of California Irvine Medical Center Chao Family SC
Orange, California, 92868
Seattle Cancer Care Alliance
Seattle, Washington, 98105
France5 sites
Novartis Investigative Site
Bordeaux, 33076
Novartis Investigative Site
Caen, 14021
Novartis Investigative Site
Marseille, 13385
Novartis Investigative Site
Nice, Alpes Maritimes, 06189
Novartis Investigative Site
Strasbourg, 67091
Japan4 sites
Novartis Investigative Site
Akashi, Hyōgo, 673-8558
Novartis Investigative Site
Fukuoka, Fukuoka, 811-1395
Novartis Investigative Site
Okayama, Okayama-ken, 700-8558
Novartis Investigative Site
Sendai, Miyagi, 980 0873
Germany3 sites
Novartis Investigative Site
Berlin, 13125
Novartis Investigative Site
Regensburg, Bavaria, 93053
Novartis Investigative Site
Tübingen, Baden-Wurttemberg, 72076
Spain3 sites
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
Madrid, 28046
Novartis Investigative Site
Seville, Andalusia, 41013
Belgium2 sites
Novartis Investigative Site
Brussels, 1090
Novartis Investigative Site
Charleroi, 6000
South Korea2 sites
Novartis Investigative Site
Seoul, Korea, 05505
Novartis Investigative Site
Seoul, 03080
Netherlands1 site
NKI-AVL, Department of Thoracic-Oncology
Amsterdam, 1066 CX
About this study
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)
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.
Read the 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.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- INC280 single agent, erlotinib
- 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)
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INC280 single agentDrug
erlotinibDrug
| Study group | Role | What they receive |
|---|---|---|
| INC280 200mg BID + ERL 150mg QD | Experimental | Subjects who took INC280 200mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD) Receives: Drug: INC280 single agent; Drug: erlotinib |
| INC280 400mg BID + ERL 150mg QD | Experimental | Subjects who took INC280 400mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD) Receives: Drug: INC280 single agent; Drug: erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination
To determine MTD and/or RP2D of INC280 in combination with erlotinib
Measured: First 28 days of dosing
Secondary outcomes (7)
Phase Ib: Overall response rate (ORR)
ORR, proportion of patients with a best overall response of complete response or partial Response (CR+PR)
Measured: Every 3 weeks, up to 5 years
Phase Ib: Disease Control Rate (DCR)
DCR, proportion of patients with best overall response of CR, PR or SD
Measured: Every 6 weeks, up to 2 years
Phase Ib: Duration of Response (DOR)
DOR, defined as time from the first documented CR or PR to first documented progression or death due to any cause
Measured: Every 6 weeks, up to 2 years
Phase Ib: Progression-free Survival (PFS)
PFS, defined as time from the first dose of study treatment to disease progression or death due to any cause
Measured: Every 6 weeks, up to 2 years
Phase Ib: Number of patients with adverse events (AEs) as a measure of safety and tolerability
Safety and tolerability of INC280 in combination with erlotinib assessed by change in vital signs, laboratory results and electrocardiogram (ECG).
Measured: Every 3 weeks, up to 2 years
Phase Ib: Plasma concentration-time profiles of INC280 and pharmacokinetic parameters
Composite pharmacokinetics of INC280 in the presence of erlotinib.
Measured: 6 weeks
Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280
Composite pharmacokinetics of erlotinib in the presence of INC280.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2015 (estimated)
- Study start23 Sep 2015
- Primary completion15 Nov 2017
- Study completion5 Dec 2018
Why it stopped: Major challenge for enrollment of participants.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02468661
- Sponsor's protocol ID
- CINC280B2201
- Other IDs
- 2015-001241-84, 2015
- Status last verified
- Feb 2020
- First submitted
- 1 Jun 2015
- Last updated
- 24 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02468661
- Acronym / sponsor ID
- CINC280B2201
- 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)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Major challenge for enrollment of participants.
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 23 Sep 2015 (actual)
- Primary completion
- 15 Nov 2017 (actual)
- Study completion
- 5 Dec 2018 (actual)
- First posted
- 11 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| INC280 200mg BID + ERL 150mg QD | Experimental | Drug: INC280 single agent, Drug: erlotinibSubjects who took INC280 200mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD) |
| INC280 400mg BID + ERL 150mg QD | Experimental | Drug: INC280 single agent, Drug: erlotinibSubjects who took INC280 400mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- Prior treatment with 3rd generation TKI
- PhaseII : Prior treatment with any of the following agents:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| INC280 single agent | Drug | INC280 200mg BID + ERL 150mg QD, INC280 400mg BID + ERL 150mg QD |
| erlotinib | Drug | INC280 200mg BID + ERL 150mg QD, INC280 400mg BID + ERL 150mg QD |
Primary outcome
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
7 secondary outcomes
Phase Ib: Overall response rate (ORR)
Time frame: Every 3 weeks, up to 5 years
Phase Ib: Disease Control Rate (DCR)
Time frame: Every 6 weeks, up to 2 years
Phase Ib: Duration of Response (DOR)
Time frame: Every 6 weeks, up to 2 years
Phase Ib: Progression-free Survival (PFS)
Time frame: Every 6 weeks, up to 2 years
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
Phase Ib: Plasma concentration-time profiles of INC280 and pharmacokinetic parameters
Time frame: 6 weeks
Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280
Time frame: 6 weeks
Results and safety
The study was stopped early (reason given: Major challenge for enrollment of participants.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
32 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing INC280 single agent and erlotinib in people with Non-Small Cell Lung Cancer, run by Novartis Pharmaceuticals at 32 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in Italy, United States, France, Japan, Germany and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Major challenge for enrollment of participants.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination (time frame: First 28 days of dosing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2020.