Clinical trial NCT03382795: Retreatment With Epidermal Growth Factor Receptor(EGFR) Tyrosine Kinase Inhibitor in EGFR Mutation Positive Patients
Official title: Retreatment With 1st Generation EGFR TKIs in Sensitizing EGFR Mutation Positive Non-Squamous Cell Carcinoma Patients Who Previously Treated With EGFR TKI and Cytotoxic Chemotherapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: EGFR Positive Non-small Cell Lung Cancer
Keywords: Epidermal growth factor receptor tyrosine kinase inhibitor
Cytotoxic chemotherapy
Epidermal growth factor receptor mutation
Lead sponsor: Korea University Guro Hospital
Sponsor class: OTHER
Collaborators: name: Chong Kun Dang Pharmaceutical Corp.
First posted: 2017-12-26
Enrollment: 63
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this trial, treatment efficacy and safety of retreatment with 1st generation epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI)s(Gefitinib/Erlotinib), will be assessed in patients with sensitizing EGFR mutation positive Non-Squamous Cell Carcinoma patients who previously treated with EGFR TKI and cytotoxic chemotherapy

Detailed description: This study is designed to be multi-center, open-label, single-arm, prospective, phase II trial of patient with sensitizing EGFR mutation positive Non-Squamous Cell Carcinoma patients who previously treated with EGFR TKI and cytotoxic chemotherapy. Approximately 69 patients will be enrolled into the trial, and expected study duration is 48 months from Institutional Review Board(IRB) and Korea Ministry of Food and Drug Safety(MFDS) approval date.

The study drug will be administered orally as one tablet(Gefitinib 250mg/ Erlotinib 150mg) once a day until disease progression or manifestation of unacceptable toxicity. The initial dose of the study drug daily can be reduced according to dose reduction criteria in protocol. A cycle of study treatment is defined as 28 days, and subjects will visit the site every 2 cycles(56 days).

Eligibility criteria: Inclusion Criteria:

1. Males or females ≥ 19 years of age
2. Non Small Cell Lung Cancer(Non-Squamous Cell Carcinoma) patients who had shown clinical benefits (Complete response(CR) or Partial response(PR) or Stable disease(SD) ≥6 months) from EGFR-TKIs as first line treatment and developed progressive disease, and then received cytotoxic chemotherapy more than 4 cycles and developed progressive disease, and then confirmed T790 negative and sensitizing EGFR mutation(E19Del, L858R, L861Q, G719X, E19insertion) positive in Histologic, cytologic specimen or blood.
3. Patient with at least one measurable lesions according to RECIST v 1.1
4. Expected life expectancy ≥ 12 weeks
5. Eastern Cooperative Oncology Group(ECOG) performance status ≤ 2
6. Patients who have proper hematologic, renal and hepatic functions as follows:

   * Absolute neutrophil count(ANC) ≥ 1,500/mm³
   * platelets ≥ 100,000/mm³
   * Hemoglobin ≥ 9g/dL
   * Total bilirubin ≤ 1.25 X UNL
   * Aspartate aminotransferase(AST or SGOT) and alanine aminotransferase(ALT or SGPT) ≤ 3.0 X UNL (if liver metastasis ≤5.0 X UNL)
   * Alkaline phosphatase ≤ 2.5 X UNL (if liver metastasis ≤5.0 X UNL)
   * Serum creatinine ≤ 1.5mg/dL
7. patients who are willing to comply with study procedure and voluntarily provide informed consent with signature

Exclusion Criteria:

1. Patients who have preexisting or coexisting malignancies in other parts except for effectively treated non-melanoma skin cancer, cervical carcinoma in situ(CIS) cervical cancer within the last 5 years
2. Patients with brain metastasis except for the followings:

   - Asymptomatic and stable brain metastases for which local treatment has been given: corticosteroids treatment isn't requiured for at least 2 weeks before starting the study treatment.
3. Patients currently receiving palliative radiation therapy or have toxicities from radiation therapy at screening.
4. Patients with clinically active history of interstitial lung disease(ILD), Drug induced ILD, Radiation pneumonitis
5. Patients with clinically significant cardiovascular disease or myocardial infarction within the past 12 months.
6. Patients with active infection or severe systemic disease that are difficult to include in this study
7. Patients who received radiation therapy to target lesion of this study.
8. Patients who had major operation within 4 weeks before starting the study treatment and were not fully recovered.
9. Patients who were administered other study drugs within 4 weeks before starting the study treatment
10. Males and females of reproductive potential who are not using an effective method of birth control and females who are pregnant or breastfeeding or have a positive pregnancy test prior to study entry
11. Patients who are difficult to include in this study in accordance with the investigator's judgment
12. Patients with histories of hypersensitivity to investigational product(IP) or any components of the agent
13. Patients with any of the following genetic predispositions including galactose intolerance, Lapp lactase deficiency, lactose intolerance or glucose-galactose malabsorption
14. Patient previously received cytotoxic chemotherapy within 2 weeks of IP administration
15. Patient received Immunotherapy prior to the study participation
16. Patients who are difficult to include in this study in accordance with the investigator's judgment due to severe adverse effects during previous EGFR TKI treatment

Primary outcomes:
measure: Objective Response Rate(ORR) including rage of CR&PR
timeFrame: Through study completion (5 years)
Secondary outcomes:
measure: Progression Free Survival, PFS
timeFrame: Through study completion (5 years)
measure: Overall Survival
timeFrame: Through study completion (5 years)
measure: The incidence of Adverse Events(including Serious Adverse Events and Adverse Drug Reactions)
timeFrame: Through study completion (5 years)
Other outcomes:
Locations:
city: Anyang
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
state: Gyeonggi-do
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
state: Gyeongsangnam-do
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeollanam-do
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
Study officials:
affiliation: Professor
name: Sung Yong Lee, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
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