Non-small Cell Lung Cancer
Conditions
Keywords
Efficacy, Safety, EGFR-TKI, phase III, NSCLC
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.
Interventions
DRUGIcotinib
125 mg three times daily (375 mg per day) by mouth
DRUGGefitinib
250 mg every 24 hours by mouth
Sponsors
Betta Pharmaceuticals Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From first study treatment until time of death | Median number of months from first study treatment until time of death |
| Best Tumor Response | 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 | 2-7 months | Median time until disease progression. Disease progression defined as radiological and/or symptomatic disease progression. |
| Safety and Tolerability | 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 |
Countries
China
Participant flow
Recruitment details
Patients were enrolled between 26 Febrary 2009 and 13 November 2010 across 27 study sites.
Participants by arm
| Arm | Count |
|---|---|
| Icotinib Icotinib 125 mg three times daily (375 mg per day) by mouth | 200 |
| Gefitinib Gefitinib 250 mg every 24 hours by mouth | 199 |
| Total | 399 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 3 |
Baseline characteristics
| Characteristic | Gefitinib | Icotinib | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 40 Participants | 36 Participants | 76 Participants |
| Age, Categorical Between 18 and 65 years | 159 Participants | 164 Participants | 323 Participants |
| Age, Continuous | 56.43 years STANDARD_DEVIATION 9.43 | 55.52 years STANDARD_DEVIATION 10.14 | 55.98 years STANDARD_DEVIATION 9.79 |
| Region of Enrollment China | 199 participants | 200 participants | 399 participants |
| Sex: Female, Male Female | 85 Participants | 82 Participants | 167 Participants |
| Sex: Female, Male Male | 114 Participants | 118 Participants | 232 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 166 / 200 | 165 / 199 |
| serious Total, serious adverse events | 13 / 200 | 15 / 199 |
Outcome results
Primary
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.
Time frame: 2-7 months
Population: All patients who received at least one dose of study drug with measurable disease at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Icotinib | Progression Free Survival | 4.6 months |
| Gefitinib | Progression Free Survival | 3.4 months |
Secondary
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
Time frame: While receiving study treatment; assessed every 21 days until progression
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Icotinib | Best Tumor Response | Partial Response (PR) | 27.1 percentage of patients |
| Icotinib | Best Tumor Response | Progressive Disease (PD) | 21.1 percentage of patients |
| Icotinib | Best Tumor Response | Stable Disease (SD) | 47.7 percentage of patients |
| Icotinib | Best Tumor Response | Disease Control (CR+PR+SD) | 75.4 percentage of patients |
| Icotinib | Best Tumor Response | Complete Response (CR) | 0.5 percentage of patients |
| Gefitinib | Best Tumor Response | Disease Control (CR+PR+SD) | 74.9 percentage of patients |
| Gefitinib | Best Tumor Response | Complete Response (CR) | 0 percentage of patients |
| Gefitinib | Best Tumor Response | Partial Response (PR) | 27.2 percentage of patients |
| Gefitinib | Best Tumor Response | Stable Disease (SD) | 47.7 percentage of patients |
| Gefitinib | Best Tumor Response | Progressive Disease (PD) | 20.5 percentage of patients |
Secondary
Overall Survival
Median number of months from first study treatment until time of death
Time frame: From first study treatment until time of death
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Icotinib | Overall Survival | 13.3 months |
| Gefitinib | Overall Survival | 13.9 months |
Secondary
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
Time frame: Assessed over two years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Icotinib | Safety and Tolerability | At least one AE | 166 participants |
| Icotinib | Safety and Tolerability | At least one SAE | 13 participants |
| Icotinib | Safety and Tolerability | At least one ADR | 121 participants |
| Icotinib | Safety and Tolerability | Grade 3 and 4 AEs | 9 participants |
| Gefitinib | Safety and Tolerability | At least one ADR | 140 participants |
| Gefitinib | Safety and Tolerability | At least one AE | 165 participants |
| Gefitinib | Safety and Tolerability | Grade 3 and 4 AEs | 10 participants |
| Gefitinib | Safety and Tolerability | At least one SAE | 15 participants |
Secondary
Time To Progression
Median time until disease progression. Disease progression defined as radiological and/or symptomatic disease progression.
Time frame: 2-7 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Icotinib | Time To Progression | 5.2 months |
| Gefitinib | Time To Progression | 3.7 months |