Preoperative Gefitinib for EGFR Mutant II-IIIa NSCLC

Sponsor

Fudan University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01833572

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Non-small-cell Lung Cancer	Drug: Gefitinib	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Single-arm, Phase II Study of Preoperative Gefitinib for Stage II-IIIa NSCLC With Activating EGFR Mutation

Study Start Date :

May 1, 2013

Anticipated Primary Completion Date :

Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gefitinib A total of 42 cases of resectable stage II-IIIA NSCLCs patients with EGFR activating mutations will be enrolled in this arm.Gefitinib 250 mg/day oral daily is given to patients after enrolment for 42 days or until disease progression or unacceptable toxicity.	Drug: Gefitinib Eligible participants will be given orally gefitinib 250mg daily before surgery for 42 days or until disease progression or unacceptable toxicity. Best supportive care is allowed in this period. Other Names: Iressa

Arm

Intervention/Treatment

Experimental: Gefitinib

A total of 42 cases of resectable stage II-IIIA NSCLCs patients with EGFR activating mutations will be enrolled in this arm.Gefitinib 250 mg/day oral daily is given to patients after enrolment for 42 days or until disease progression or unacceptable toxicity.

Drug: Gefitinib

Eligible participants will be given orally gefitinib 250mg daily before surgery for 42 days or until disease progression or unacceptable toxicity. Best supportive care is allowed in this period.

Other Names:

Iressa

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) [at day 42 of gefitinib treatment]

Secondary Outcome Measures

Pathologic response rate [Pathologic response rate is depended on the pathology dignosis after surgery, an expected average of 8 weeks from enrollment.]
Complete resection rate [Complete resection rate is depended on the pathology dignosis after surgery, an expected average of 8 weeks from enrollment.]
Number of participants with adverse events [During the neoadjuvant and perioperative period, an expected average of 10 weeks from enrollment]
Quality of life (QoL) [During the neoadjuvant period, an expected average of 6 weeks from enrollment]
Disease free survival (DFS) [Participants after surgery will receive long-term follow-up for up to 5 years]
Overall survival (OS) [Participants after surgery will receive long-term follow-up for up to 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Provision of informed consent
Pathologically confirmed non-small cell lung cancer with EGFR exon 19 deletion or exon 21 L858 mutation.
Clinically or pathologically confirmed stage II-IIIA
Tolerable to complete resection of lung cancer
Male or female aged 18 years and over
Able to comply with the required protocol and follow-up procedures, and able to receive oral medications
ECOG performance status 0-1.
Life expectancy ≥12 weeks.
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).
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).
Adequate renal function: Serum creatinine ≤ 1.5 x upper limit of normal (ULN), and creatinine clearance≥ 60 ml/min.
Measurable disease according to the preset criteria .

Exclusion Criteria:

Known severe hypersensitivity to gefitinib or any of the excipients of this product
Any serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study
Interstitial lung disease(ILD) or pulmonary fibrosis; impaired pulmonary function (e.g. FEV1 <40% predicted value, artery blood gas PaO2<60mmHg)
Patients with prior exposure to agents directed at the HER axis (e.g. erlotinib, gefitinib, cetuximab, trastuzumab).
Patients with prior exposure to chemotherapy, irradiation or systemic anti-cancer therapy (e.g. monoclonal antibody therapy) for lung cancer.
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.
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).
Eye inflammation or eye infection not fully treated or predisposing factor of this.
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.
Patient who has serious active infection
Patients who harbouring exon 20 T790M mutation.
Pregnancy or breast feeding.