NOV120101 Phase 2 Study in NSCLC Patients With Aquired Resistance to 1st Generation EGFR Tyrosine Kinase Inhibitors

NCT ID: NCT01718847

Last Updated: 2015-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2014-09-30

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 2nd line monotherapy agent in lung adenocarcinoma patients with acquired resistance to prior EGFR tyrosine kinase inhibitors (TKIs).

Detailed Description

Acquired resistance to prior EGFR TKIs is considered as "unmet medical need" in clinical practice. To evaluate the efficacy of NOV120101 (Poziotinib) as a second-line monotherapeutic agent, patients with acquired resistance to gefitinib or erlotinib will be enrolled in this study. Subjects will receive NOV120101 (Poziotinib) 16 mg PO once daily until disease progression or unacceptable toxicity development. Progression free survival (PFS) will be analyzed as the primary endpoint in this trial. Secondary endpoints including PFS rate at 16 weeks, ORR and DCR will also be analyzed.

Conditions

Increased Drug Resistance

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NOV120101 (Poziotinib)

16 mg PO once daily until disease progression or unacceptable toxicity development

Group Type: EXPERIMENTAL

NOV120101 (Poziotinib)

Intervention Type: DRUG

16 mg PO once daily until disease progression or unacceptable toxicity development

Interventions

NOV120101 (Poziotinib)

16 mg PO once daily until disease progression or unacceptable toxicity development

Intervention Type: DRUG

Other Intervention Names

HM781-36B

Eligibility Criteria

Inclusion Criteria

1. Male or female patients aged 20 years or older

2. Pathologically confirmed stage IIIB (unresectable) or IV lung adenocarinoma

3. Patients who have 1 or more than 1 measurable or evaluable but unmeasurable lesions according to RECIST ver1.1

4. Patients who received prior 1st generation EGFR TKIs (gefitinib or erlotinib) monotherapy and meet the following criteria:

1. Patients with EGFR mutation (e.g., G719X, exon 19 deletion, L858R, L861Q, etc) known to be associated with sensitivity to TKIs

2. Patients who showed objective clinical benefit from treatment with an EGFR TKI as defined by either:

• Patients who showed complete (CR) or partial response (PR), or
• Patients who maintained stable disease (SD) status ≥ 6 months

3. Patients who showed progressive disease (PD, RECIST ver1.1) while on continuous treatment with gefitinib or erlotinib within the last 30 days (However, patients whose progressive disease is limited in the brain cannot participate in this trial.)

4. No intervening systemic chemotherapy between cessation of the EGFR TKI and participation of this study

5. Patients who agree to the collection of tumor tissue specimen

6. ECOG performance status ≤ 2

7. Life expectancy of ≥ 12 weeks

8. Adequate hematological, hepatic and renal functions:

WBC ≥ 4,000/mm3, Platelet ≥ 100,000/mm3, Serum creatinine ≤ 1.5 X ULN, AST and ALT ≤ 2.5 X ULN, Total bilirubin ≤ 1.5 X ULN

9. Patients who give written informed consent voluntarily

Exclusion Criteria

1. Patients who receive IP within 3 days from prior treatment with gefitinib or erlotinib

2. NCI-CTCAE grade > 1 adverse events due to treatment with gefitinib or erlotinib

3. Prior systemic chemo, immuno, hormonal and/or biological therapy except gefitinib or erlotinib within 4 weeks before IP administration

4. Acquired resistance to EGFR TKI due to conversion of adenocarcinoma into small cell lung cancer

5. Patients who received major surgery within 4 weeks before IP administration

6. Symptomatic CNS metastases (patients with radiologically and neurologically stable metastases and being off corticosteroids for at least 4 weeks are able to participate in this trial.)

7. 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 and considered to be cured by investigator's judgment

8. Known pre-existing interstitial lung disease (ILD)

9. 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

10. 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%.)

11. Patients with known active hepatitis B, HIV infection, or other uncontrolled infectious disease

12. Clinically significant or recent acute gastrointestinal disorders with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption disorders, CTCAE grade ≥ 2 diarrhea due to any etiology)

13. Patients who cannot receive IP by mouth and be diagnosed with clinically significant gastrointestinal disorders which can prevent administration, transit or absorption of the IP

14. Pregnancy or breast-feeding

15. 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

16. Patients who received other investigational products except gefitinib and erlotinib within 4 weeks before participation

17. Patients who cannot participate in this trial by investigator's judgment

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hanmi Pharmaceutical Company Limited

INDUSTRY

Sponsor Role: collaborator

National OncoVenture

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ji-Youn Han, MD. Ph.D

Role: STUDY_CHAIR

National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea,Asan Medical Center, Songpa-gu, Seoul, Republic of Korea,

Ki Hyeong Lee, MD, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Chungbuk National University Hospital, Cheongju-si, Chungcheongbuk-do, Republic of Korea

Sang-We Kim, MD, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Asan Medical Center, Songpa-gu, Seoul, Republic of Korea

Young Joo Min, MD, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Ulsan University Hospital, Dong-gu, Ulsan, Republic of Korea

Eunkyung Cho, MD, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Gachon University Gil Medical Center, Incheon, Republic of Korea

Locations

National Cancer Center

Goyang-si, Gyeonggi-do, South Korea

Chungbuk National University Hospital

Cheongju-si, North Chungcheong, South Korea

Asan Medical Center

Songpa-gu, Seoul, South Korea

Ulsan University Hospital

Dong-gu, Ulsan, South Korea

Gachon University Gil Medical Center

Incheon, , South Korea

Countries

South Korea

Other Identifiers

NOV120101-202

Identifier Type: -

Identifier Source: org_study_id