Clinical trial NCT02526537: Gefitinib for EGFR Sensitive Mutation Postoperative Stage Ib NSCLC Patients
Official title: The Postoperative Adjuvant Therapy of Gefitinib for High Risk Stage Ib NSCLC Patients With EGFR Sensitive Mutation, an Open, Paired, Non-interventional, Multi-center Clinical Study
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: NSCLC
Keywords: Gefitinib
NSCLC
postoperative
stage Ib
Relapse Free Survival in 2 years
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2015-08-18
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 78
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: NSCLC patients received complete resection at stage Ib with deletion of exon 19 or mutation of L858R at exon 21 in EGFR

Brief summary: Currently, whether adjuvant therapy should be applied to Stage Ib non-small cell lung cancer (NSCLC) patients who received radical resection remains controversial. There is still no clear evidence that the postoperative adjuvant chemotherapy or other treatments can improve the survival rate for patients with stage Ib NSCLC. Tyrosine Kinase Inhibitors (TKIs) such as Gefitinib and Erlotinib are widely accepted as the first-line therapy for Epidermal growth factor receptor (EGFR) gene mutation late stage NSCLC patients. However the effect is largely uncertain for early stage patients who received surgery. The investigators aim to evaluate the effect of postoperative adjuvant use of Gefitinib for high risk stage Ib EGFR sensitive mutation NSCLC patients.

Detailed description: Currently, whether adjuvant therapy should be applied to Stage Ib non-small cell lung cancer (NSCLC) patients who received radical resection remains controversial. CALGB9633 studies have shown that for patients with stage Ib NSCLC who received radical resection, postoperative adjuvant chemotherapy does not benefit for all patients, only patients with high risk (cancer diameter \>4cm) can benefit. There is still no clear evidence that the postoperative adjuvant chemotherapy or other treatments can improve the survival rate for patients with stage Ib NSCLC.

The EGFR gene mutation rate is about 10% for European patients, and about 30-40% for patients of Asian origins. In a retrospective observation study of 1118 stage I to stage III NSCLC patients who received surgery, D'Angelo et al. found that the risk of death for patients with EGFR sensitive mutation is lower than those without mutation. The authors indicated that postoperative use of TKI for EGFR sensitive mutation patients might be the possible reason. Since the mutation rate of EGRF gene is higher in Asian patients, compared with patients of other origins, the investigators speculate that Asian patients might benefit for postoperative use of TKIs.

EGFR gene mutation detection is routinely prescribed nowadays for lung adenocarcinoma patients who received surgical resection. According to NCCN guideline, stage IB patients with high risk factors are recommended to receive adjuvant chemotherapy. For patients who can not tolerate or decline chemotherapy, non-specific treatment ( Chinese herbal medicine and nonspecific immunomodulators as adjuvant anti-cancer treatment for 2 years) is recommended, otherwise, TKIs（Gefitinib 250 mg daily for 2 years) is also an alternative choice if the cancer has EGFR sensitive mutation. Based on patient's own choice of postoperative adjuvant therapy , the patients were enrolled for observation of prognosis.

Eligibility criteria: Inclusion Criteria:

1. High-risk who meet one of the following descriptions: 1). Poorly differentiated carcinoma (including neuroendocrine tumors); 2). Vascular invasion; 3). Tumor diameter≥4cm 5). Visceral pleura involvement.
2. Patients with pathology confirmed Ib stage NSCLC
3. Patients with deletion of exon 19 or mutation of L858R at exon 21 in EGFR gene
4. ECOG score of 0-1
5. Life expectancy over 12 weeks
6. Absolute neutrophil count (ANC) \>= 1.75 x 109 / L, platelet \>= 100 x 109 / L, hemoglobin is more than or equal to 9 g / dl
7. Total bilirubin \<= the normal value of 1.5 times the upper limit of normal (ULN); liver metastases, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) \<= 2.5 times of upper limit of normal (ULN)
8. Serum creatinine \<=1.25 times of the upper limit of normal value, creatinine clearance rate \> 60 or ml/min
9. received the informed consent from patient or his/her legal representative

Exclusion Criteria:

1. Patients who was serious allergy to any of the ingredients of drugs used in this study
2. Patients who unable to comply with the study plan or research program;
3. Patients with severe systemic disease that the researchers judged will be unable to complete the study;
4. Patients have severe heart disease, such as myocardial infarction within 6 months;
5. Patients have interstitial pneumonia;
6. Patients who were confirmed to be positive pathology for cutting edge;
7. The preoperative chest CT showed nodules \>= 50%, and showed ground glass opacity;
8. Patients received wedge resection;
9. Patients used HER2 pathways involved drugs such as erlotinib, gefitinib, cetuximab rituximab, trastuzumab)
10. Patients who have received chemotherapy or systemic antitumor therapy (such as monoclonal antibody therapy);
11. Patients received radiotherapy;
12. Having other malignant tumors in the last 5 years, but not including who has been cured through surgery and survived 5 year of disease-free;
13. Any unstable systemic diseases (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction, serious arrhythmias, liver, kidney or metabolic diseases within six months).
14. Patients who do not get effective treatment of inflammation, eye infections or predisposing factors;
15. Physical examination or laboratory findings evidence reasonable doubt who is ill or use of related drugs could affect the study;
16. Patients with serious active infections;
17. Patients with T790M mutations at 20 exon;
18. Woman who are pregnant or lactating.

Primary outcomes:
measure: Relapse Free Survival in 2 years
timeFrame: Treatment period: 2 years (24 months)
Secondary outcomes:
measure: Relapse Free Survival in 3 years
timeFrame: Follow-up: 3 years
measure: 5 year Overall Survival
timeFrame: Follow-up: 5 years
measure: Relapse Free Survival in 5 years
timeFrame: Follow-up: 5 years
Other outcomes:
Locations:
city: ChengDu
country: China
facility: West China Hospital
state: Sichuan
Study officials:
affiliation: West China Hospital
name: Lunxu Liu, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wu YL, Zhong WZ, Li LY, Zhang XT, Zhang L, Zhou CC, Liu W, Jiang B, Mu XL, Lin JY, Zhou Q, Xu CR, Wang Z, Zhang GC, Mok T. Epidermal growth factor receptor mutations and their correlation with gefitinib therapy in patients with non-small cell lung cancer: a meta-analysis based on updated individual patient data from six medical centers in mainland China. J Thorac Oncol. 2007 May;2(5):430-9. doi: 10.1097/01.JTO.0000268677.87496.4c.
citation: Strauss GM, Herndon JE 2nd, Maddaus MA, Johnstone DW, Johnson EA, Harpole DH, Gillenwater HH, Watson DM, Sugarbaker DJ, Schilsky RL, Vokes EE, Green MR. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008 Nov 1;26(31):5043-51. doi: 10.1200/JCO.2008.16.4855. Epub 2008 Sep 22.
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