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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01610336




Registration number
NCT01610336
Ethics application status
Date submitted
3/04/2012
Date registered
4/06/2012
Date last updated
22/06/2020

Titles & IDs
Public title
A Safety and Efficacy Study of INC280 and Gefitinib in Patients With EGFR Mutated, c-MET-amplified NSCLC Who Have Progressed After EGFRi Treatment
Scientific title
A Phase IB/II, Open Label, Multicenter Study of INC280 Administered Orally in Combination With Gefitinib in Adult Patients With EGFR Mutated, c-MET-amplified Non-small Cell Lung Cancer Who Have Progressed After EGFR Inhibitor Treatment
Secondary ID [1] 0 0
2011-002569-39
Secondary ID [2] 0 0
CINC280X2202
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - INC280

Experimental: INC280+gefitinib - INC280+gefitinib


Treatment: Drugs: INC280
experimental
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase Ib: Frequency and characteristics of dose limiting toxicities (DLTs) to the - 1 cycle= 28 days
Timepoint [1] 0 0
From date of treatment until DLT, up to 52weeks
Primary outcome [2] 0 0
Phase II : Overall Response Rate of tumors per RECIST 1.1
Timepoint [2] 0 0
from date of treatment until disease progression, up to 100 weeks
Secondary outcome [1] 0 0
Overall survival (OS) - OS is defined as the time from the date of treatment to the date of death from any cause.
Timepoint [1] 0 0
From date of treatment until death, up to 5 years
Secondary outcome [2] 0 0
Frequency, duration, and severity of adverse events (AEs) - Safety via monitoring of AEs
Timepoint [2] 0 0
30 days post study treatment
Secondary outcome [3] 0 0
Inhibition of c-MET signaling by pre- and post- treatment immunohistochemistry of p-c-MET, - 1 cycle= 28 days
Timepoint [3] 0 0
Day 15 of cycle 1
Secondary outcome [4] 0 0
Plasma concentration of INC280 - 1 cycle= 28 days
Timepoint [4] 0 0
Day 1 of cycle 4
Secondary outcome [5] 0 0
Progression free survival (PFS) - PFS is defined as the time from the date of treatment to the date of event defined as the first documented progression per RECIST or death due to any cause.
Timepoint [5] 0 0
From date of treatment to the date of disease progression, up to 5 years
Secondary outcome [6] 0 0
Plasma concentration of gefitinib - 1 cycle= 28 days
Timepoint [6] 0 0
Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4
Secondary outcome [7] 0 0
PK parameters AUC - 1 cycle= 28 days
Timepoint [7] 0 0
Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4
Secondary outcome [8] 0 0
PK parameters Cmax - 1 cycle= 28 days
Timepoint [8] 0 0
Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4
Secondary outcome [9] 0 0
PK parameters Tmax - 1 cycle= 28 days
Timepoint [9] 0 0
Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4
Secondary outcome [10] 0 0
PK parameters accumulation ration - 1 cycle= 28 days
Timepoint [10] 0 0
Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4
Secondary outcome [11] 0 0
PK parameters half- life - 1 cycle= 28 days
Timepoint [11] 0 0
Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4
Secondary outcome [12] 0 0
number of SAE, and severity of serious adverse events (SAEs) - Safety via monitoring SAEs
Timepoint [12] 0 0
30 days post study treatment
Secondary outcome [13] 0 0
number of AE - via monitoring changes in physical examination, clinical laboratory parameters, vital signs and ECGs
Timepoint [13] 0 0
30 days post study treatment

Eligibility
Key inclusion criteria
- Documented EGFR mutation

- Documented c-MET dysregulation

- Prior clinical benefit on EGFR inhibitors and then subsequent progression

-= 18 year old

- Life expectancy of = 3 months

- ECOG performance status = 2
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Unable to swallow tables once or twice daily

- Previous treatment with c-MET inhibitor

- Any unresolved toxicity form previous anticancer therapy greater than grade 1

- History of cystic fibrosis

- History of acute or chronic pancreatitis

- Unable to undergo MRI or CT sans

- Known history of HIV

- Undergone a bone marrow or solid organ transplant

- Clinically significant wound or lung tumor lesions with increased likelihood of
bleeding

- Pregnant or nursing

Other protocol-defined inclusion/exclusion criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/04/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/05/2020
Sample size
Target
Accrual to date
Final
161
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Woolloongabba
Recruitment hospital [2] 0 0
Novartis Investigative Site - Bedford Park
Recruitment hospital [3] 0 0
Novartis Investigative Site - East Bentleigh
Recruitment hospital [4] 0 0
Novartis Investigative Site - Auckland
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment postcode(s) [3] 0 0
3165 - East Bentleigh
Recruitment postcode(s) [4] 0 0
- Auckland
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Leuven
Country [2] 0 0
China
State/province [2] 0 0
Guangdong
Country [3] 0 0
China
State/province [3] 0 0
Shanghai
Country [4] 0 0
China
State/province [4] 0 0
Beijing
Country [5] 0 0
China
State/province [5] 0 0
Guangzhou
Country [6] 0 0
France
State/province [6] 0 0
Strasbourg Cedex
Country [7] 0 0
France
State/province [7] 0 0
Toulouse Cedex 9
Country [8] 0 0
Germany
State/province [8] 0 0
Frankfurt
Country [9] 0 0
Germany
State/province [9] 0 0
Freiburg
Country [10] 0 0
Israel
State/province [10] 0 0
Haifa
Country [11] 0 0
Israel
State/province [11] 0 0
Ramat Gan
Country [12] 0 0
Israel
State/province [12] 0 0
Tel Aviv
Country [13] 0 0
Italy
State/province [13] 0 0
BO
Country [14] 0 0
Italy
State/province [14] 0 0
MI
Country [15] 0 0
Italy
State/province [15] 0 0
MO
Country [16] 0 0
Japan
State/province [16] 0 0
Aichi
Country [17] 0 0
Japan
State/province [17] 0 0
Tokyo
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Korea
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Seocho Gu
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Seoul
Country [21] 0 0
Netherlands
State/province [21] 0 0
AZ
Country [22] 0 0
Netherlands
State/province [22] 0 0
Amsterdam
Country [23] 0 0
Netherlands
State/province [23] 0 0
Rotterdam
Country [24] 0 0
Singapore
State/province [24] 0 0
Singapore
Country [25] 0 0
Spain
State/province [25] 0 0
Andalucia
Country [26] 0 0
Spain
State/province [26] 0 0
Catalunya
Country [27] 0 0
Spain
State/province [27] 0 0
Madrid
Country [28] 0 0
Taiwan
State/province [28] 0 0
Tainan
Country [29] 0 0
Taiwan
State/province [29] 0 0
Taipei
Country [30] 0 0
Thailand
State/province [30] 0 0
THA
Country [31] 0 0
Thailand
State/province [31] 0 0
Bangkok

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will assess the safety and efficacy of escalating doses INC280 when added to
gefitinib in patients with lung cancer that are known to have dysregulation of the c-MET
pathway and who have failed after benefiting on a prior treatment with either gefitinib or
erlotinib.
Trial website
https://clinicaltrials.gov/show/NCT01610336
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications