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

NCT01718847 | Completed Phase 2 DMC

• 1 other identifier: NOV120101-202
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

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).

Conditions

Increased Drug Resistance

Keywords

EGFR Tyrosine Kinase Inhibitor; Aquired resistance to EGFR TKI; Pan-Her inhibitor

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  The length of time during and after medication or treatment during which the disease being treated (usually cancer) does not get worse.

  By 1 year after enrollment of the last subject

Secondary Outcomes (9)

• PFS rate at 16 weeks

  16 weeks

• Objective response rate (ORR)

  By 1 year after enrollment of the last subject

• Disease control rate (DCR)

  By 1 year after enrollment of the last subject

• Overall survival (OS)

  By 1 year after enrollment of the last subject

• Time to progression (TTP)

  By 1 year after enrollment of the last subject

Other Outcomes (2)

• Population pharmacokinetics (PK) of NOV120101 (Poziotinib)

  By 3 months after enrollment of the last subject

• Subgroup analyses with the genetic information

  by 1 year after enrollment of the last patient

Study Arms (1)

NOV120101 (Poziotinib)

EXPERIMENTAL

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

Drug: NOV120101 (Poziotinib)

Interventions

NOV120101 (Poziotinib) DRUG

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

Also known as: HM781-36B

NOV120101 (Poziotinib)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 20 years or older
• Pathologically confirmed stage IIIB (unresectable) or IV lung adenocarinoma
• Patients who have 1 or more than 1 measurable or evaluable but unmeasurable lesions according to RECIST ver1.1
• Patients who received prior 1st generation EGFR TKIs (gefitinib or erlotinib) monotherapy and meet the following criteria:
• Patients with EGFR mutation (e.g., G719X, exon 19 deletion, L858R, L861Q, etc) known to be associated with sensitivity to TKIs
• 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
• 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.)
• No intervening systemic chemotherapy between cessation of the EGFR TKI and participation of this study
• Patients who agree to the collection of tumor tissue specimen
• ECOG performance status ≤ 2
• Life expectancy of ≥ 12 weeks
• 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

You may not qualify if:

• Patients who receive IP within 3 days from prior treatment with gefitinib or erlotinib
• NCI-CTCAE grade \> 1 adverse events due to treatment with gefitinib or erlotinib
• Prior systemic chemo, immuno, hormonal and/or biological therapy except gefitinib or erlotinib within 4 weeks before IP administration
• Acquired resistance to EGFR TKI due to conversion of adenocarcinoma into small cell lung cancer
• Patients who received major surgery within 4 weeks before IP administration
• 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.)
• 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
• Known pre-existing interstitial lung disease (ILD)
• 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
• 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%.)
• Patients with known active hepatitis B, HIV infection, or other uncontrolled infectious disease
• 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)
• 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
• Pregnancy or breast-feeding
• 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

Sponsors & Collaborators

• National OncoVenture: lead
• Hanmi Pharmaceutical Company Limited: collaborator

Study Sites (5)

National Cancer Center

Goyang-si, Gyeonggi-do, 410-769, South Korea

Location

Chungbuk National University Hospital

Cheongju-si, North Chungcheong, 361-711, South Korea

Location

Asan Medical Center

Songpa-gu, Seoul, 138-736, South Korea

Location

Ulsan University Hospital

Dong-gu, Ulsan, 682-714, South Korea

Location

Gachon University Gil Medical Center

Incheon, 405-760, South Korea

Location

MeSH Terms

Interventions

HM781-36B

Study Officials

• Ji-Youn Han, MD. Ph.D

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

  STUDY CHAIR

• Ki Hyeong Lee, MD, Ph.D

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

  PRINCIPAL INVESTIGATOR

• Sang-We Kim, MD, Ph.D

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

  PRINCIPAL INVESTIGATOR

• Young Joo Min, MD, Ph.D

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

  PRINCIPAL INVESTIGATOR

• Eunkyung Cho, MD, Ph.D

  Gachon University Gil Medical Center, Incheon, Republic of Korea

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2012
• First Posted: October 31, 2012
• Study Start: January 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: August 14, 2015

Record last verified: 2015-08

Locations

KR (5)