Safety and Efficacy Study of Icotinb in Non-small Cell Lung Cancer (NSCLC) Patients (ICOGEN)

• Overall Survival [ Time Frame: From first study treatment until time of death ] [ Designated as safety issue: No ]
  Median number of months from first study treatment until time of death
• Best Tumor Response [ Time Frame: While receiving study treatment; assessed every 21 days until progression ] [ Designated as safety issue: No ]
  Change in size of tumor: Complete Response (CR) = no measurable tumor; Partial Response (PR) = 30% decrease in size of measurable tumor; Stable Disease (SD) = measurable tumor size has not changed; Progressive Disease (PD) = measurable tumor larger than at baseline
• Time To Progression [ Time Frame: 2-7 months ] [ Designated as safety issue: No ]
  Median time until disease progression. Disease progression defined as radiological and/or symptomatic disease progression.
• Safety and Tolerability [ Time Frame: Assessed over two years ] [ Designated as safety issue: Yes ]

  Adverse Events (AEs) and Serious AEs (SAEs) are presented regardless of causality for patients who received at least one dose of Icotinib or Gefitinib. Events were graded by the investigator using the NCI CTCAE Scale (version 3.0) which provides a grading scale for each AE term.

  Grade 3 = Severe Grade 4 = Life-threatening or disabling

• all cause mortality [ Time Frame: 6 months -1 year ] [ Designated as safety issue: No ]
• response evaluation [ Time Frame: 3-6 months ] [ Designated as safety issue: No ]
• all cause progress [ Time Frame: 3-6 months ] [ Designated as safety issue: No ]
• Health-Related Quality of Life (HR QOL) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
• all cause adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

The purpose of this study is to determine whether Icotinib is at least non-inferior to Gefitinib in the treatment of advanced non-small cell lung cancer (NSCLC) patients after one or two chemotherapies.

Lung cancer is the rapidest increased type of cancer in China with over 5 times incidence rate increase during the past 30 years . It is the leading cause of death of cancer in man and 2nd in women. With the development of gefitinib and erlotinib, EGFR-TKI (epidermal growth factor receptor -tyrosine kinase inhibitor) is the most successful novel drugs developed for the treatment of these patients in recent years, especially for NSCLC patients in Asia including China. Icotinib is a novel EGFR-TKI developed by a group of Chinese scientists and clinician. It appears to be at least as good as gefitinib in terms of efficacy and better in terms of safety in phase I/II trials. In this study, a randomized, double-blind, gefitinib as control, multi-center phase III trial was designed to evaluate the safety and efficacy of icotinib in the treatment of advanced NSCLC patients after failure of 1 or 2 chemotherapy. PFS (progress free survival) is the primary end-point with OS (overall survival), ORR (objective response), TTP (time to progress), HRQOL and safety as the secondary end-point. A total of 400 patients will be recruited. EGFR and K-ras gene mutational analysis as well as a population PK study have also been proposed.

• Drug: Icotinib
  125 mg three times daily (375 mg per day) by mouth
  Other Names:

  • BPI-2009
  • Conmana
• Drug: Gefitinib
  250 mg every 24 hours by mouth
  Other Names:

  • ZD1839
  • Iressa

• Experimental: Icotinib
  125 mg three times daily (375 mg per day) by mouth
  Intervention: Drug: Icotinib
• Active Comparator: Gefitinib
  250 mg every 24 hours by mouth
  Intervention: Drug: Gefitinib

Inclusion Criteria:

1. Confirmed NSCLC with Histology or cytology; advanced （IIIb/IV).
2. Must have received 1 or 2 chemotherapy (at least 1 is platin based)before, and prior chemotherapy must be completed at least 4 weeks before study enrollment; =.

Exclusion Criteria:

1. Previous usage of EGFR-TKI or antibody to EGFR: gefitinib, erlotinib, herceptin, erbitux.