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.

Tracking Information

• First Submitted Date: December 27, 2009
• First Posted Date: December 30, 2009
• Results First Submitted Date: February 21, 2012
• Results First Posted Date: May 24, 2012
• Last Update Posted Date: February 14, 2014
• Study Start Date: February 2009
• Actual Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 27, 2012)

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.

• Original Primary Outcome Measures (submitted: December 29, 2009): all cause progress or mortality [ Time Frame: 3-6 months ]

Current Secondary Outcome Measures (submitted: April 23, 2012)

• Overall Survival [ Time Frame: From first study treatment until time of death ]
  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 ]
  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 ]
  Median time until disease progression. Disease progression defined as radiological and/or symptomatic disease progression.
• 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

Original Secondary Outcome Measures (submitted: December 29, 2009)

• all cause mortality [ Time Frame: 6 months -1 year ]
• response evaluation [ Time Frame: 3-6 months ]
• all cause progress [ Time Frame: 3-6 months ]
• Health-Related Quality of Life (HR QOL) [ Time Frame: 1 year ]
• all cause adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 1 year ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy Study of Icotinb in Non-small Cell Lung Cancer (NSCLC) Patients
• 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
• 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.
• 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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer

Intervention

• 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

Study Arms

• 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

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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 23, 2012): 399
• Original Actual Enrollment (submitted: December 29, 2009): 400
• Actual Study Completion Date: December 2011
• Actual Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT01040780
• Other Study ID Numbers: BPI-2009
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Betta Pharmaceuticals Co., Ltd.
• Original Responsible Party: Yan Sun/Professor/M.D., Cancer Hospital,Chinese Academy Of Medical Sciences
• Current Study Sponsor: Betta Pharmaceuticals Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

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.

• PRS Account: Betta Pharmaceuticals Co., Ltd.
• Verification Date: January 2014