Clinical trial NCT01833572: Preoperative Gefitinib for EGFR Mutant II-IIIa NSCLC (ECTOP-1001)
Official title: A Single-arm, Phase II Study of Preoperative Gefitinib for Stage II-IIIa NSCLC With Activating EGFR Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-small-cell Lung Cancer
Keywords: epidermal growth factor receptor
EGFR mutation
Tyrosine kinase inhibitor
gefitinib
neo-adjuvant therapy
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2013-04-17
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a clinical trial from Eastern Cooperative Thoracic Oncology Project (ECTOP), numbered as ECTOP-1001. This is an open-label, single-arm, phase II interventional clinical trial. The investigators hypothesize that the application of EGFR-TKI, like gefitinib will be efficient and safe in a neo-adjuvant setting. 42 resectable stage II-IIIa NSCLC patients with EGFR activating (19/21) mutations will be eligible to be enrolled. EGFR mutation will be prospectively tested in all the participants' biopsy samples and confirmed in surgical resected samples. Eligible patients will be given gefitinib 250mg for 42days followed with surgical resection of tumor. Efficacy of preoperative gefitinib is based on radiographic (CT response/ORR), pathologic (pathologic response), surgical (complete resection) evaluations, and safety is based on adverse effect evaluations.


Eligibility criteria: Inclusion Criteria:

1. Provision of informed consent
2. Pathologically confirmed non-small cell lung cancer with EGFR exon 19 deletion or exon 21 L858 mutation.
3. Clinically or pathologically confirmed stage II-IIIA
4. Tolerable to complete resection of lung cancer
5. Male or female aged 18 years and over
6. Able to comply with the required protocol and follow-up procedures, and able to receive oral medications
7. ECOG performance status 0-1.
8. Life expectancy ≥12 weeks.
9. Adequate hematological function: Absolute neutrophil count (ANC) ≥2.0 x 109/L, and Platelet count ≥100 x 109/L, and Hemoglobin ≥9 g/dL (may be transfused to maintain or exceed this level).
10. Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN); Aspartate amino transferase (AST) and alanine amino transferase (ALT) ≤ 2.5 x upper limit of normal (ULN).
11. Adequate renal function: Serum creatinine ≤ 1.5 x upper limit of normal (ULN), and creatinine clearance≥ 60 ml/min.
12. Measurable disease according to the preset criteria .

Exclusion Criteria:

1. Known severe hypersensitivity to gefitinib or any of the excipients of this product
2. Any serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study
3. Interstitial lung disease(ILD) or pulmonary fibrosis; impaired pulmonary function (e.g. FEV1 \<40% predicted value, artery blood gas PaO2\<60mmHg)
4. Patients with prior exposure to agents directed at the HER axis (e.g. erlotinib, gefitinib, cetuximab, trastuzumab).
5. Patients with prior exposure to chemotherapy, irradiation or systemic anti-cancer therapy (e.g. monoclonal antibody therapy) for lung cancer.
6. Previous or current malignancies of other histologies within the last 5 years with the exception of the following: other malignancies cured by surgery alone and having a continuous disease-free survival of 5 years; cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix.
7. Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within six months, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).
8. Eye inflammation or eye infection not fully treated or predisposing factor of this.
9. Evidence of any other disease, neurological or metabolic dysfunction, physical examination or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the subject at high risk for treatment-related complications.
10. Patient who has serious active infection
11. Patients who harbouring exon 20 T790M mutation.
12. Pregnancy or breast feeding.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: at day 42 of gefitinib treatment
Secondary outcomes:
measure: Pathologic response rate
timeFrame: Pathologic response rate is depended on the pathology dignosis after surgery, an expected average of 8 weeks from enrollment.
measure: Complete resection rate
timeFrame: Complete resection rate is depended on the pathology dignosis after surgery, an expected average of 8 weeks from enrollment.
measure: Number of participants with adverse events
timeFrame: During the neoadjuvant and perioperative period, an expected average of 10 weeks from enrollment
measure: Quality of life (QoL)
timeFrame: During the neoadjuvant period, an expected average of 6 weeks from enrollment
measure: Disease free survival (DFS)
timeFrame: Participants after surgery will receive long-term follow-up for up to 5 years
measure: Overall survival (OS)
timeFrame: Participants after surgery will receive long-term follow-up for up to 5 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
Study officials:
affiliation: Fudan Univerisity Shanghai Cancer Center
name: Haiquan Chen, MD
role: PRINCIPAL_INVESTIGATOR
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