Adenocarcinoma of Lung Stage IIIB, Adenocarcinoma of Lung Stage IV
Conditions
Keywords
EGFR mutation, Lung Adenocarcinoma, Firstline therapy, Second generation of tyrosine kinase
Brief summary
The purpose of this open-label, single-arm, multi-center phase II trial is to evaluate the efficacy and safety of novel pan-HER inhibitor, NOV120101 (Poziotinib), as a first-line monotherapeutic agent in patients with lung adenocarcinoma harboring EGFR mutation.
Detailed description
EGFR TKIs are known as more effective and less toxic medications against EGFR mutated tumors. However, newly acquired resistance to these inhibitors is the inevitable obstacle in continuous treatment with them. To overcome this problem, many new class of TKIs including NOV120101 (Poziotinib) are developing these days. To evaluate the efficacy of NOV120101 (Poziotinib) as a first-line monotherapeutic medication, chemotherapy-naïve patients will participate in this study. Subjects will receive NOV120101 (Poziotinib) 12 mg PO once daily until disease progression or unacceptable toxicity development. Objective response rate (ORR) will be analyzed as the primary endpoint in this trial. Secondary endpoints including PFS rate at 12 months, DCR, PFS, and OS will also be analyzed.
Interventions
NOV120101 (Poziotinib)12 mg PO once daily until disease progression or unacceptable toxicity development
Sponsors
Hanmi Pharmaceutical Company Limited
National OncoVenture
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients aged 20 years or older 2. Pathologically confirmed stage IIIB (unresectable) or IV lung adenocarcinoma 3. Documented EGFR mutation (e.g., exon 19 deletion, exon 21 L858R, etc.) with tumor tissue 4. Patients who have 1 or more measurable lesions according to RECIST version 1.1 5. ECOG performance status 2 or less 6. Life expectancy of 12 weeks or more 7. Patients who have adequate hematological, hepatic and renal functions; WBC 4,000 or more per mm3, platelet 100,000 or more per mm3, serum creatinine 1.5 times or less upper limit of normal, AST and ALT 2.5 times or less upper limit of normal, total bilirubin 1.5 times or less upper limit of normal 8. Patients who give written informed consent voluntarily
Exclusion criteria
1. Prior systemic chemotherapy, immunotherapy or biological therapy for stage IIIB or IV adenocarcinoma (However, neo or adjuvant chemo, chemoradio or radiotherapy is permitted if at least 6 months has elapsed prior to disease progression) 2. Prior treatment with small molecules or antibodies targeting EGFR 3. Patients who received major surgery within 4 weeks before study drug administration 4. Symptomatic CNS metastases (patients with radiologically and neurologically stable metastases and being off corticosteroids for at least 2 weeks are able to participate in this trial.) 5. History of other malignancies except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for 3 years or more and considered to be cured by investigator's judgment 6. Known preexisting interstitial lung disease (ILD) 7. NYHA class III or IV heart failure, uncontrolled hypertension, unstable angina or myocardial infarction within 6 months, poorly controlled arrhythmia or other clinically significant cardiovascular abnormalities at investigator's discretion 8. Patients whose left ventricle ejection fraction (LVEF) is below the institutional lower limit of normal (if no lower limit of normal is defined in the site, the lower limit is 50 percent) 9. Patients with known active hepatitis B, HIV infection, or other uncontrolled infectious disease 10. Clinically significant or recent acute gastrointestinal disorders with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption disorders, CTCAE grade 2 diarrhea or more due to any etiology) 11. Patients who cannot receive IP by mouth and be diagnosed with clinically significant gastrointestinal disorders which can prevent administration, transit or absorption of the study drug 12. Pregnancy or breast feeding 13. Women of childbearing potential (WOCBP) or men who are unwilling to use adequate contraception or be abstinent during the trial and for at least 2 months after the end of treatment 14. Patients who received other investigational products except gefitinib and erlotinib within 4 weeks before participation 15. Patients who cannot participate in this trial by investigator's judgment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | about 3 years | the proportion of patients with complete response (CR) and/or partial response (PR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) rate at 12 months | 12 months after enrollment of the last subject | the proportion of patients with complete response (CR) and/or partial response (PR) at 12 months following start of study drug administration. |
| Disease control rate (DCR) | 3 years | the proportion of patients with CR, PR and/or stable disease (SD) |
| Progression free survival (PFS) | 3 years | The length of time during and after medication or treatment during which the disease being treated (usually cnacer) does not get worse. |
| Overall survival (OS) | 3 years | the time from study drug administration until death from any cause |
| Change of quality of life (QoL) measured by EQ-5D questionnaire | 3 years | Change means the end of treatment minus baseline in each patient |
Other
| Measure | Time frame | Description |
|---|---|---|
| Population pharmacokinetics (PK) of NOV120101 (Poziotinib) | 3 months after enrollment of the last subject | to observe pharmacokinetic parameter, inter-individual variability and intra-individual variability considering covariates, demographic factors, influencing PK profile. |
| Subgroup analyses according to the genetic information | 3 years | to observe HGF expression status in plasma and T790M mutation induction status from plasma DNA |
Countries
South Korea
Outcome results
None listed