NOV120101 (Poziotinib) for 1st Line Monotherapy in Patients With Lung Adenocarcinoma

A Prospective, Open-label, Single Arm, Multi-center, Phase II Exploratory Trial to Evaluate the Efficacy and Safety of NOV120101 (Poziotinib) as the First-line Treatment Medication in Patients With Harboring EGFR Mutations

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.

Study Overview

• Status: Terminated
• Conditions: Adenocarcinoma of Lung Stage IV; Adenocarcinoma of Lung Stage IIIB
• Intervention / Treatment: Drug: NOV120101 (Poziotinib)

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769
      • National Cancer Center
  • Incheon,
    • Namdong-Gu, Incheon,, Korea, Republic of, 405-760
      • Gachon University Gil Hospital
  • Seoul
    • Gangnam-gu, Seoul, Korea, Republic of, 135-710
      • Samsung Medical Center
    • Jongno-gu, Seoul, Korea, Republic of, 110-744
      • Seoul National University Hospital
    • Songpa-gu, Seoul, Korea, Republic of, 136-738
      • Asan Medical Center
  • Ulsan
    • Dong-gu, Ulsan, Korea, Republic of, 682-714
      • Ulsan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: NOV120101 (Poziotinib); Single arm study with NOV120101(poziotinib)12mg PO daily administration	Drug: NOV120101 (Poziotinib); NOV120101 (Poziotinib)12 mg PO once daily until disease progression or unacceptable toxicity development; Other Names: Poziotinib; HM781-36B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	the proportion of patients with complete response (CR) and/or partial response (PR)	about 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS) rate at 12 months	the proportion of patients with complete response (CR) and/or partial response (PR) at 12 months following start of study drug administration.	12 months after enrollment of the last subject
Disease control rate (DCR)	the proportion of patients with CR, PR and/or stable disease (SD)	3 years
Progression free survival (PFS)	The length of time during and after medication or treatment during which the disease being treated (usually cnacer) does not get worse.	3 years
Overall survival (OS)	the time from study drug administration until death from any cause	3 years
Change of quality of life (QoL) measured by EQ-5D questionnaire	Change means the end of treatment minus baseline in each patient	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Population pharmacokinetics (PK) of NOV120101 (Poziotinib)	to observe pharmacokinetic parameter, inter-individual variability and intra-individual variability considering covariates, demographic factors, influencing PK profile.	3 months after enrollment of the last subject
Subgroup analyses according to the genetic information	to observe HGF expression status in plasma and T790M mutation induction status from plasma DNA	3 years

Collaborators and Investigators

• Sponsor: National OncoVenture
• Collaborators: Hanmi Pharmaceutical Company Limited
• Investigators: Study Director: Jungyong Kim, MD, National OncoVenture

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (ACTUAL): November 1, 2015
• Study Completion (ACTUAL): November 1, 2015

Study Registration Dates

• First Submitted: March 14, 2013
• First Submitted That Met QC Criteria: March 24, 2013
• First Posted (ESTIMATE): March 27, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): March 1, 2016
• Last Update Submitted That Met QC Criteria: February 26, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Lung Adenocarcinoma; EGFR mutation; Firstline therapy; Second generation of tyrosine kinase
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenocarcinoma; Adenocarcinoma of Lung
• Other Study ID Numbers: NOV120101-201