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 Amplificatio
- Registration Number
- CTRI/2016/09/007293
- Lead Sponsor
- ovartis Healthcare Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Suspended
- Sex
- Not specified
- Target Recruitment
- 0
Patients must have received one and only one prior line of 1st generation (eg
erlotinib, gefitinib) or 2nd generation (afatinib) EGFR TKI for the treatment of
locally advanced or metastatic NSCLC
2. No prior chemotherapy is allowed, except in the following instances:
Patients, who switched from platinum-based chemotherapy to EGFR TKI during
first line treatment within 28 days since the start date of chemotherapy, will be
allowed to enter the study, in the absence of disease progression
3. Prior neoadjuvant/adjuvant cytotoxic chemotherapy is not allowed, unless the
relapse occurred more than 12 months
4.Molecular pre-screening assessment
cMET-amplification (GCN more than 6) by FISH determined by a Novartis-designated central
laboratory on a newly obtained tumor biopsy (preferred) or an archival tumor sample
obtained at or any time after the progression on prior 1st or 2nd generation EGFR TKI
5. EGFRT790M negative status assessed from a biopsy or an archival tumor sample
collected at or any time after the progression on prior 1st or 2nd generation EGFR TKI,
determined locally by either Roche Cobas or Qiagen therascreen test or by a Novartisdesignated
central laboratory
6. Presence of at least one measurable lesion according to RECIST v1.1. A previously
irradiated site lesion may only be counted as a target lesion if there is clear sign of
progression since the irradiation
More than 18 years of age at the time of informed consent.
Locally advanced or metastatic NSCLC (stage IIIB and is not a candidate for definitive
multimodality therapy or IV) other than predominantly squamous cell histology harboring
EGFR mutation known to be associated with EGFR TKI drug sensitivity (exon 19 deletion
or L858R).
Patients must meet the criteria for acquired resistance to EGFR TKI (either 1st generation
(eg erlotinib, gefitinib) or 2nd generation (eg, afatinib)) defined as
Documented clinical benefit (CR, PR, or SD (= 6 months) as per RECIST)
Demonstrated progression, while on continuous treatment, or within 30 days since the
date of last administration of EGFR TKI, per RECIST
Patients must have recovered from all toxicities related to prior anticancer therapies to
grade more 1 (CTCAE v 403). Patients with any grade of alopecia are allowed to enter the
study.
Life expectancy more than 3 months
Patients eligible for the Phase II of this study must not meet any of the following criteria
Patients with history of severe hypersensitivity reaction to platinum containing drugs,
pemetrexed or any known excipients of these drugs.
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.
Thoracic radiotherapy to lung fields less than 4 weeks prior to study enrollment or patients who
have not recovered from radiotherapy related toxicities. For all other anatomic sites
including radiosurgery for brain metastasis, radiotherapy to thoracic vertebrae and ribs,
radiotherapy less than 2 weeks prior to starting study treatment or patients who have not
recovered from radiotherapy related toxicities
Presence or history of a malignant disease other than NSCLC that has been diagnosed
And or required therapy within the past 3 years. Exceptions to this exclusion include the
Following completely resected basal cell and squamous cell skin cancers, indolent
malignancies that currently do not require treatment, and completely resected carcinoma
in situ of any type
Presence of clinically significant ophthalmologic abnormalities that might increase the
risk of corneal epithelial injury, such as severe dry eye syndrome, keratoconjunctivitis
sicca, Sjogrens syndrome, and severe exposure keratopathy.
Bullous and exfoliative skin disorders at baseline of any grade
Presence or history of microangiopathic hemolytic anemia with thrombocytopenia.
Clinically significant, uncontrolled heart diseases and or recent cardiac event within 6
months prior to screening, such as
Unstable angina within 6 months prior to screening
Myocardial infarction within 6 months prior to screening
History of documented congestive heart failure New York Heart Association
functional classification 3 and 4
Ventricular arrhythmias
upraventricular and nodal arrhythmias not controlled with medication
Other cardiac arrhythmia not controlled with medication
QTCF more than 450 msec
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Phase II: Progression-free Survival (PFS) [ Time Frame: Every 6 weeks, up to 2 years ]Timepoint: Every 6 weeks, up to 2 years
- Secondary Outcome Measures
Name Time Method Overall Response Rate (ORR) by investigators assessment according to RECIST v1.1 Time Frame: Every 6 weeks, up to 2 yearsTimepoint: Every 6 weeks, up to 2 years;Overall Survival (OS) [ Time Frame: Every 3 weeks, up to 5 years ]Timepoint: Every 3 weeks, up to 5 years;To characterize the PK of erlotinib in the presence <br/ ><br>of INC280Timepoint: 6 weeks;To characterize the PK of INC280 and its <br/ ><br>metabolite CMN288 in the presence of erlotinibTimepoint: 6 weeks;To characterize the PK of INC280 and its <br/ ><br>metabolite CMN288 single agentTimepoint: 6 weeks;To determine safety and tolerability of INC280 <br/ ><br>single agentTimepoint: Every 3 weeks up to 2 years;To determine safety and tolerability of the <br/ ><br>combination of INC280 and erlotinibTimepoint: 6 weeks