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

A Randomized,Double-blind,Multicenter Phase III Trial to Evaluate the Safety and Efficacy of Icotinib and Gefitinib in Advanced NSCLC Patients Previously Treated With Chemotherapy

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.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Icotinib; Drug: Gefitinib

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 399
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Chinese PLA General Hospital
    • Beijing, Beijing, China, 100020
      • Beijing Chao-Yang Hospital
    • Beijing, Beijing, China, 100032
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China, 100071
      • 307 Hospital of PLA
    • Beijing, Beijing, China, 101149
      • Beijing Chest Hospital
    • Beijing, Beijing, China, 100021
      • Cancer Hospital, Chinese Academy of Medical Science
    • Beijing, Beijing, China, 100036
      • Bejing Cancer Hospital
    • Beijing, Beijing, China, 100079
      • Peking University Third Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400042
      • Third Affiliated Hospital, Third Military Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital, Southern Medical University
    • Guangzhou, Guangdong, China, 510080
      • Guangdong General Hospital
    • Guangzhou, Guangdong, China, 510000
      • Guanghzou General Hospital of PLA
    • Guanzhou, Guangdong, China, 510060
      • Sun Yat-Sen Univerisity Cancer Center
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
    • Changsha, Hunan, China, 410011
      • The second Xiangya Hospital,Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Jiangsu Cancer Hospital
    • Nanjing, Jiangsu, China, 210002
      • 81 Hospital of PLA
    • Nanjing, Jiangsu, China, 210002
      • Nanjing General Hospital of Nanjing Command，PLA
  • Jilin
    • Changchun, Jilin, China, 130012
      • Jilin cancer hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Shanghai Pulmonary Hospital
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital,Fudan University
    • Shanghai, Shanghai, China, 200433
      • Changhai Hospital, Second Military Medical University
    • Shanghai, Shanghai, China, 200023
      • Ruijin Hospital，Shanghai Jiao-Tong University
  • Shanxi
    • Xi-An, Shanxi, China, 710032
      • Xijing hospital, Fourth military medical university
    • Xi-an, Shanxi, China, 710000
      • Tangdu Hospital, Fourth Military Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310022
      • The First Affiliated Hospital of College of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Icotinib; 125 mg three times daily (375 mg per day) by mouth	Drug: Icotinib; 125 mg three times daily (375 mg per day) by mouth; Other Names: BPI-2009; Conmana
Active Comparator: Gefitinib; 250 mg every 24 hours by mouth	Drug: Gefitinib; 250 mg every 24 hours by mouth; Other Names: Iressa; ZD1839

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline.	2-7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Median number of months from first study treatment until time of death	From first study treatment until time of death
Best Tumor Response	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	While receiving study treatment; assessed every 21 days until progression
Time To Progression	Median time until disease progression. Disease progression defined as radiological and/or symptomatic disease progression.	2-7 months
Safety and Tolerability	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	Assessed over two years

Collaborators and Investigators

• Sponsor: Betta Pharmaceuticals Co., Ltd.
• Investigators: Principal Investigator: Li Zhang, M.D., Sun Yat-sen University; Principal Investigator: Yan Sun, M.D., Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Study Director: Fenlai Tan, M.D./Ph.D., Zhejiang Betapharma Inc.

Publications and helpful links

General Publications

• Shi Y, Zhang L, Liu X, Zhou C, Zhang L, Zhang S, Wang D, Li Q, Qin S, Hu C, Zhang Y, Chen J, Cheng Y, Feng J, Zhang H, Song Y, Wu YL, Xu N, Zhou J, Luo R, Bai C, Jin Y, Liu W, Wei Z, Tan F, Wang Y, Ding L, Dai H, Jiao S, Wang J, Liang L, Zhang W, Sun Y. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial. Lancet Oncol. 2013 Sep;14(10):953-61. doi: 10.1016/S1470-2045(13)70355-3. Epub 2013 Aug 13.
• Camidge DR. Icotinib: kick-starting the Chinese anticancer drug industry. Lancet Oncol. 2013 Sep;14(10):913-4. doi: 10.1016/S1470-2045(13)70385-1. Epub 2013 Aug 13. No abstract available.
• Zhao Q, Shentu J, Xu N, Zhou J, Yang G, Yao Y, Tan F, Liu D, Wang Y, Zhou J. Phase I study of icotinib hydrochloride (BPI-2009H), an oral EGFR tyrosine kinase inhibitor, in patients with advanced NSCLC and other solid tumors. Lung Cancer. 2011 Aug;73(2):195-202. doi: 10.1016/j.lungcan.2010.11.007. Epub 2010 Dec 8.
• Tan F, Shen X, Wang D, Xie G, Zhang X, Ding L, Hu Y, He W, Wang Y, Wang Y. Icotinib (BPI-2009H), a novel EGFR tyrosine kinase inhibitor, displays potent efficacy in preclinical studies. Lung Cancer. 2012 May;76(2):177-82. doi: 10.1016/j.lungcan.2011.10.023. Epub 2011 Nov 22.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: December 27, 2009
• First Submitted That Met QC Criteria: December 29, 2009
• First Posted (Estimate): December 30, 2009

Study Record Updates

• Last Update Posted (Estimate): February 14, 2014
• Last Update Submitted That Met QC Criteria: January 21, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Safety; NSCLC; Efficacy; phase III; EGFR-TKI
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Gefitinib
• Other Study ID Numbers: BPI-2009