Non-small Cell Lung Cancer Clinical Trial
Official 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
Verified date | March 2021 |
Source | Novartis |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This study assessed the safety and efficacy of escalating doses INC280 when added to gefitinib in patients with lung cancer that were known to have dysregulation of the c-MET pathway and who had failed after benefiting on a prior treatment with either gefitinib or erlotinib.
Status | Completed |
Enrollment | 161 |
Est. completion date | May 27, 2020 |
Est. primary completion date | June 10, 2016 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 Exclusion Criteria: - Unable to swallow tables once or twice daily - Previous treatment with c-MET inhibitor - Any unresolved toxicity from previous anticancer therapy greater than grade 1 - History of cystic fibrosis - History of acute or chronic pancreatitis - Unable to undergo MRI or CT scans - 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 |
Country | Name | City | State |
---|---|---|---|
Australia | Novartis Investigative Site | Auckland | |
Australia | Novartis Investigative Site | East Bentleigh | Victoria |
Australia | Novartis Investigative Site | Woolloongabba | Queensland |
Belgium | Novartis Investigative Site | Leuven | |
China | Novartis Investigative Site | Beijing | |
China | Novartis Investigative Site | Guangzhou | |
China | Novartis Investigative Site | Guangzhou | Guangdong |
China | Novartis Investigative Site | Shanghai | Shanghai |
France | Novartis Investigative Site | Strasbourg Cedex | |
France | Novartis Investigative Site | Toulouse Cedex 9 | |
Germany | Novartis Investigative Site | Frankfurt | |
Germany | Novartis Investigative Site | Freiburg | |
Israel | Novartis Investigative Site | Ramat Gan | |
Italy | Novartis Investigative Site | Milano | MI |
Italy | Novartis Investigative Site | Milano | MI |
Italy | Novartis Investigative Site | Modena | MO |
Japan | Novartis Investigative Site | Koto ku | Tokyo |
Korea, Republic of | Novartis Investigative Site | Gyeonggi do | Korea |
Korea, Republic of | Novartis Investigative Site | Seoul | Korea |
Korea, Republic of | Novartis Investigative Site | Seoul | Seocho Gu |
Korea, Republic of | Novartis Investigative Site | Seoul | |
Korea, Republic of | Novartis Investigative Site | Seoul | |
Netherlands | Novartis Investigative Site | Amsterdam | |
Netherlands | Novartis Investigative Site | Maastricht | AZ |
Netherlands | Novartis Investigative Site | Rotterdam | |
Singapore | Novartis Investigative Site | Singapore | |
Spain | Novartis Investigative Site | Barcelona | Catalunya |
Spain | Novartis Investigative Site | Madrid | |
Taiwan | Novartis Investigative Site | Tainan | |
Taiwan | Novartis Investigative Site | Taipei | |
Thailand | Novartis Investigative Site | Bangkok |
Lead Sponsor | Collaborator |
---|---|
Novartis Pharmaceuticals |
Australia, Belgium, China, France, Germany, Israel, Italy, Japan, Korea, Republic of, Netherlands, Singapore, Spain, Taiwan, Thailand,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Phase I: Percentage of Change From Baseline in C-MET H Score at Cycle 1 Day 15 | Inhibition of c-MET signaling by pre- and post- treatment immunohistochemistry of p-c-MET | Baseline, Day 15 of cycle 1 (Cycle=28days) | |
Primary | Phase Ib: Frequency of Dose Limiting Toxicities (DLTs) | A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol. | Up to 215 weeks | |
Primary | Phase II : Overall Response Rate (ORR) | Overall response rate is defined as the proportion of patients with best overall response (BOR) of complete response (CR) or partial response (PR), as per RECIST 1.1 (Overall Response (OR) = CR + PR). Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. |
Until disease progression, up to 60.8 weeks | |
Secondary | Phase Ib and II: Number of Participants With Adverse Events (AEs) | Adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 | Up to 421 weeks | |
Secondary | Phase Ib and II: Number of Participants With Serious Adverse Events (SAEs) | Serious adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 | Up to 421 weeks | |
Secondary | Phase Ib and II: Number of Patients With Dose Reductions of INC280 by Dose Level | Number of patients with dose reductions of INC280 by dose level as a measure of tolerability. | Up to 417 weeks | |
Secondary | Phase Ib and II: Number of Patients With Dose Interruptions of Gefitinib by Dose Level | Number of patients with dose interruptions of gefitinib by dose level as a measure of tolerability | Up to 417 weeks | |
Secondary | Phase II: Overall Survival (OS) | Overall survival is defined as the time from the start of treatment date to the date of death, due to any cause | From date of treatment until death due to any cause, up to 70.2 months | |
Secondary | Phase II: Progression Free Survival (PFS) | Progression-free survivalis the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. | Up to 60.8 months | |
Secondary | Phase II: Duration of Response (DoR) | Duration of overall response (DOR) is defined as the time between the date of first documented response (CR or PR) and the date of first documented disease progression or death due to underlying cancer. | Up to 23.2 months | |
Secondary | Phase I: PK Parameters AUCtau of INC280 and Gefitinib | PK parameters were estimated from each individual plasma concentration-time profile using non-compartmental analysis. Area under the plasma concentration-time curve (AUC) from time zero to the end of dosing interval at steady state (tau), where tau=24 hours for once daily dosing and tau=12 hours for twice daily dosing |
Cycle 1 day 15 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose) (Cycle=28 days) | |
Secondary | Phase I: PK Parameters Cmax of INC280 and Gefitinib | PK parameters were estimated from each individual plasma concentration-time profile using non-compartmental analysis. Cmax is the maximum observed plasma concentration of INC280 and gefitinib |
Cycle 1 day 15 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose) (Cycle=28 days) | |
Secondary | Phase I: PK Parameters Tmax of INC280 and Gefitinib | PK parameters were estimated from each individual plasma concentration-time profile using non-compartmental analysis. Tmax is the time to reach maximum plasma concentration of INC280 and gefitinib |
Cycle 1 day 15 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose) (Cycle=28 days) | |
Secondary | Phase I: PK Parameters Apparent Systemic Plasma Clearance Rate of INC280 and Gefitinib | PK parameters were estimated from each individual plasma concentration-time profile using non-compartmental analysis. Apparent systemic plasma clearance rate of INC280 and gefitinib |
Cycle 1 day 15 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose) (Cycle=28 days) | |
Secondary | Phase I: PK Parameters Half-life of INC280 and Gefitinib | PK parameters were estimated from each individual plasma concentration-time profile using non-compartmental analysis. The elimination half-life of INC280 and gefitinib associated with the terminal slope (Lamda_z) of a semi-logarithmic plasma concentration-time curve |
Cycle 1 day 15 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose)(Cycle=28 days) |
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
NCT03087448 -
Ceritinib + Trametinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer (NSCLC)
|
Phase 1 | |
Recruiting |
NCT05042375 -
A Trial of Camrelizumab Combined With Famitinib Malate in Treatment Naïve Subjects With PD-L1-Positive Recurrent or Metastatic Non-Small Cell Lung Cancer
|
Phase 3 | |
Completed |
NCT02526017 -
Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers
|
Phase 1 | |
Enrolling by invitation |
NCT00068003 -
Harvesting Cells for Experimental Cancer Treatments
|
||
Terminated |
NCT05414123 -
A Therapy Treatment Response Trial in Patients With Leptomeningeal Metastases ((LM) Using CNSide
|
||
Recruiting |
NCT05059444 -
ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation
|
||
Recruiting |
NCT05919537 -
Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation
|
Phase 1 | |
Recruiting |
NCT05009836 -
Clinical Study on Savolitinib + Osimertinib in Treatment of EGFRm+/MET+ Locally Advanced or Metastatic NSCLC
|
Phase 3 | |
Recruiting |
NCT03412877 -
Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer
|
Phase 2 | |
Active, not recruiting |
NCT03170960 -
Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors
|
Phase 1/Phase 2 | |
Completed |
NCT03219970 -
Efficacy and Safety of Osimertinib for HK Chinese With Metastatic T790M Mutated NSCLC-real World Setting.
|
||
Recruiting |
NCT05949619 -
A Study of BL-M02D1 in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer or Other Solid Tumors
|
Phase 1/Phase 2 | |
Recruiting |
NCT04054531 -
Study of KN046 With Chemotherapy in First Line Advanced NSCLC
|
Phase 2 | |
Withdrawn |
NCT03519958 -
Epidermal Growth Factor Receptor (EGFR) T790M Mutation Testing Practices in Hong Kong
|
||
Completed |
NCT03384511 -
The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
|
Phase 4 | |
Terminated |
NCT02580708 -
Phase 1/2 Study of the Safety and Efficacy of Rociletinib in Combination With Trametinib in Patients With mEGFR-positive Advanced or Metastatic Non-small Cell Lung Cancer
|
Phase 1/Phase 2 | |
Completed |
NCT01871805 -
A Study of Alectinib (CH5424802/RO5424802) in Participants With Anaplastic Lymphoma Kinase (ALK)-Rearranged Non-Small Cell Lung Cancer (NSCLC)
|
Phase 1/Phase 2 | |
Terminated |
NCT04042480 -
A Study of SGN-CD228A in Advanced Solid Tumors
|
Phase 1 | |
Recruiting |
NCT05919641 -
LIVELUNG - Impact of CGA in Patients Diagnosed With Localized NSCLC Treated With SBRT
|
||
Completed |
NCT03656705 -
CCCR-NK92 Cells Immunotherapy for Non-small Cell Lung Carcinoma
|
Phase 1 |