Phase II Clinical Study of Intermittent High Dose of Icotinib in Combination With Docetaxel to Treat Lung Cancer

Single Arm, Phase II Clinical Study of Intermittent High Dose of Icotinib in Combination With Docetaxel as Second-line Treatment for Non-small Cell Lung Cancer Patients With Wild Type EGFR:

1. There is as yet no optimal treatment regimen for patients with epidermal growth factor receptor (EGFR) gene wild type non-small-cell lung cancer (NSCLC) .
2. Icotinib is a new type of small molecule EGFR TKI, developed and patented by Zhejiang BetaPharma Co., Ltd.(Hangzhou, Zhejiang, China, Patent No. WO2003082830). It has the similar anti-tumor activity with gefitinib, erlotinib. Pre-clinical studies showed icotinib could significantly inhibit the EGFR tyrosine kinase activity. Notably, anti-tumor activities were observed in patients with advanced NSCLC.
3. In this study, we will evaluate the efficiency of intermittent high dose of Icotinib in combination with Docetaxel as second-line treatment for NSCLC patients with wild type EGFR. The overall response rate(ORR),progression free survival(PFS) ,overall survival(OS) and health related quality of life(HRQoL) will be monitored.

Inclusion Criteria:

• Histologically or cytologically confirmed stage IIIB/IV NSCLC patients progressing after first-line chemotherapy;
• Patients must have stopped prior platinum-based therapy at least four weeks prior to enroll and fully recovered from chemotherapy-induced toxicity;
• Age: 18-70 years old;
• Patients with wild-type EGFR;
• With a histologically or cytologically confirmed measurable disease (longest diameters >=10mm with Spiral computed tomography (CT)and >=20mm with conventional CT) according to Response Evaluation Criteria in Solid Tumors (RECIST Criteria);
• Patients must have Eastern Cooperative Oncology Group(ECOG)Performance Status of 0-2;
• Must have an expected survival time of at least 12 weeks;
• Patients should have adequate bone marrow function defined as an absolute peripheral neutrophil count (ANC) of ≥1.5 ´ 109/L, platelet count of ≥ 75´ 109/L; Hemoglobin(Hb) ≥ 9g/dL;
• adequate hepatic function: bilirubin ≤2x the upper limit of normal, glutamic-oxaloacetic transaminase(AST )and glutamate pyruvate transaminase(ALT)≤2x the upper limit of normal (≤5x the upper limit of normal if evidence of liver metastases);
• adequate renal function: bilirubin serum creatinine ≤1.5 x the upper limit of normal;
• No malabsorption or other gastrointestinal disorders affecting drug absorption;
• Female patients of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to study entry.Male patients must use at least one reliable form of contraception during treatment and within 3 months after treatment;
• Patients have provided a signed Informed Consent Form.

Exclusion Criteria:

• Experience of Anti-EGFR Monoclonal Antibody or small molecular compounds therapy such as gefitinib, cetuximab, erlotinib or trastuzumab;
• Concomitant use with phenytoin, carbamazepine, rifampicin, phenobarbital or St. John's Wort;
• Allergic to icotinib or any of the excipients of this product.
• Prior chemotherapy with any paclitaxel agents;
• Central nervous system (CNS) metastases without radiotherapy and/or surgery;
• Evidence of clinically active Interstitial lung diseases;
• Severe systemic disease out of control such as unstable or uncompensated respiratory,cardiac,liver,renal diseases;
• Patient has a concurrent malignancy or has a malignancy within 5 years of study enrollment, (with the exception of non melanoma skin cancer or cervical carcinoma in situ);
• Psychiatric illness that would prevent the patient from giving informed consent;
• Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the study;
• Patient is concurrently using other approved or investigational antineoplastic agent;
• Pregnant or lactating women;
• Positive epidermal growth factor receptor mutation.