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

• ClinicalTrials.gov Identifier: NCT01040780
• Recruitment Status: Completed
• First Posted: December 30, 2009
• Results First Posted: May 24, 2012
• Last Update Posted: February 14, 2014
• Sponsor: Betta Pharmaceuticals Co., Ltd.
• Information provided by (Responsible Party): Betta Pharmaceuticals Co., Ltd.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Drug: Icotinib; Drug: Gefitinib	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 399 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: February 2009
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: December 2011

Arms and Interventions

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: ZD1839; Iressa

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival [ Time Frame: 2-7 months ]
   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.

Secondary Outcome Measures :

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

   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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

China, Beijing

Beijing Chao-Yang Hospital

Beijing, Beijing, China, 100020

Cancer Hospital, Chinese Academy of Medical Science

Beijing, Beijing, China, 100021

Peking Union Medical College Hospital

Beijing, Beijing, China, 100032

Bejing Cancer Hospital

Beijing, Beijing, China, 100036

307 Hospital of PLA

Beijing, Beijing, China, 100071

Peking University Third Hospital

Beijing, Beijing, China, 100079

Chinese PLA General Hospital

Beijing, Beijing, China, 100853

Beijing Chest Hospital

Beijing, Beijing, China, 101149

China, Chongqing

Third Affiliated Hospital, Third Military Medical University

Chongqing, Chongqing, China, 400042

China, Guangdong

Guanghzou General Hospital of PLA

Guangzhou, Guangdong, China, 510000

Guangdong General Hospital

Guangzhou, Guangdong, China, 510080

Nanfang Hospital， Southern Medical University

Guangzhou, Guangdong, China, 510515

Sun yat-sen Univerisity Cancer Center

Guanzhou, Guangdong, China, 510060

China, Hunan

the Second Xiangya Hospital，Central South University

Changsha, Hunan, China, 410011

Hunan Cancer Hospital

Changsha, Hunan, China, 410013

China, Jiangsu

81 Hospital of PLA

Nanjing, Jiangsu, China, 210002

Nanjing General Hospital of Nanjing Command，PLA

Nanjing, Jiangsu, China, 210002

Jiangsu Cancer Hospital

Nanjing, Jiangsu, China, 210009

China, Jilin

Jilin Cancer Hospital

Changchun, Jilin, China, 130012

China, Shanghai

Ruijin Hospital，Shanghai Jiao-Tong University

Shanghai, Shanghai, China, 200023

Zhongshan Hospital，Fudan University

Shanghai, Shanghai, China, 200032

Changhai Hospital， Second Military Medical University

Shanghai, Shanghai, China, 200433

Shanghai Pulmonary Hospital

Shanghai, Shanghai, China, 200433

China, Shanxi

Tangdu Hospital, Fourth Military Medical University

Xi-an, Shanxi, China, 710000

Xijing Hospital, Fourth Military Medical University

Xi-An, Shanxi, China, 710032

China, Zhejiang

The First Affiliated Hospital of College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China, 310022

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China, 310022

Sponsors and Collaborators

Betta Pharmaceuticals Co., Ltd.

Investigators

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

More Information

Publications of Results:

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.

Other Publications:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Betta Pharmaceuticals Co., Ltd.
• ClinicalTrials.gov Identifier: NCT01040780
• Other Study ID Numbers: BPI-2009
• First Posted: December 30, 2009
• Results First Posted: May 24, 2012
• Last Update Posted: February 14, 2014
• Last Verified: January 2014

Keywords provided by Betta Pharmaceuticals Co., Ltd.:

Efficacy; Safety; EGFR-TKI; phase III; NSCLC

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Gefitinib; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents