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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Hanmi Pharmaceutical Company Limited
Information provided by (Responsible Party):
National OncoVenture
ClinicalTrials.gov Identifier:
NCT01718847
First received: October 22, 2012
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

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).


Condition Intervention Phase
Increased Drug Resistance
Drug: NOV120101 (Poziotinib)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Exploratory Trial to Evaluate the Efficacy and Safety of NOV120101 (Poziotinib) in Lung Adenocarcinoma Patients With Acquired Resistance to 1st Generation EGFR Tyrosine Kinase Inhibitors

Resource links provided by NLM:


Further study details as provided by National OncoVenture:

Primary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: By 1 year after enrollment of the last subject ] [ Designated as safety issue: No ]
    The length of time during and after medication or treatment during which the disease being treated (usually cancer) does not get worse.


Secondary Outcome Measures:
  • PFS rate at 16 weeks [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    The proportion of Patients maintaining progress-free status at 16 weeks

  • Objective response rate (ORR) [ Time Frame: By 1 year after enrollment of the last subject ] [ Designated as safety issue: No ]
    The proportion of patients with partial response or complete response at their best tumor treatment evaluation

  • Disease control rate (DCR) [ Time Frame: By 1 year after enrollment of the last subject ] [ Designated as safety issue: No ]
    The proportion of patients with CR, PR and/or stable disease (SD)

  • Overall survival (OS) [ Time Frame: By 1 year after enrollment of the last subject ] [ Designated as safety issue: No ]
  • Time to progression (TTP) [ Time Frame: By 1 year after enrollment of the last subject ] [ Designated as safety issue: No ]
  • Time to objective response [ Time Frame: By 1 year after enrollment of the last subject ] [ Designated as safety issue: No ]
  • Duration of objective response [ Time Frame: By 1 year after enrollment of the last subject ] [ Designated as safety issue: No ]
  • Duration of disease control [ Time Frame: By 1 year after enrollment of the last subject ] [ Designated as safety issue: No ]
  • Change of quality of life (QoL) measured by EQ-5D questionnaire [ Time Frame: baseline and the end of treatment, by 1 year after enrollment of the last subject ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Population pharmacokinetics (PK) of NOV120101 (Poziotinib) [ Time Frame: By 3 months after enrollment of the last subject ] [ Designated as safety issue: No ]
    The study of the sources and correlates of variability in drug concentrations among individuals who are the target patient population receiving clinically relevant doses of a study drug. Certain patient demographic, pathophysiological, and therapeutical features, such as body weight, excretory and metabolic functions, and the presence of other therapies, can regularly alter dose-concentration relationships.

  • Subgroup analyses with the genetic information [ Time Frame: by 1 year after enrollment of the last patient ] [ Designated as safety issue: No ]
    Subgroup analysis, in the context of design and analysis of study drug, refers to looking for pattern in a subset of the subjects according to genotype


Estimated Enrollment: 40
Study Start Date: January 2013
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NOV120101 (Poziotinib)
16 mg PO once daily until disease progression or unacceptable toxicity development
Drug: NOV120101 (Poziotinib)
16 mg PO once daily until disease progression or unacceptable toxicity development
Other Name: HM781-36B

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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01718847

Locations
Korea, Republic of
Chungbuk National University Hospital
Cheongju-si,, Chungcheongbuk-do, Korea, Republic of, 361-711
National Cancer Center
Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769
Asan Medical Center
Songpa-gu, Seoul, Korea, Republic of, 138-736
Ulsan University Hospital
Dong-gu, Ulsan, Korea, Republic of, 682-714
Sponsors and Collaborators
National OncoVenture
Hanmi Pharmaceutical Company Limited
Investigators
Study Chair: Jiyoun Han, MD. Ph.D National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea,Asan Medical Center, Songpa-gu, Seoul, Republic of Korea,
Principal Investigator: Kihyoung Lee, MD, Ph.D Chungbuk National University Hospital, Cheongju-si, Chungcheongbuk-do, Republic of Korea
Principal Investigator: Daeho Lee, MD, Ph.D Asan Medical Center, Songpa-gu, Seoul, Republic of Korea
Principal Investigator: Youngju Min, MD, Ph.D Ulsan University Hospital, Dong-gu, Ulsan, Republic of Korea
  More Information

No publications provided

Responsible Party: National OncoVenture
ClinicalTrials.gov Identifier: NCT01718847     History of Changes
Other Study ID Numbers: NOV120101-202
Study First Received: October 22, 2012
Last Updated: July 3, 2014
Health Authority: Korea: Food and Drug Administration

Keywords provided by National OncoVenture:
EGFR Tyrosine Kinase Inhibitor
Aquired resistance to EGFR TKI
Pan-Her inhibitor

ClinicalTrials.gov processed this record on October 22, 2014