Vinorelbine-ifosfamide Versus Gefitinib for EGFR Gene Mutation Negative Non-small Cell Lung Cancer Patients
In the National Comprehensive Cancer Network (NCCN) guideline for NSCLC, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is recommended as the third-line treatment for EGFR gene mutation negative NSCLC patients who failed to the first-line platinum doublet chemotherapy [i.e. paclitaxel-carboplatin (PC) or gemcitabine-cisplatin (GP)] and the second-line chemotherapy with docetaxel or pemetrexed. But as we know, if patients had no EGFR gene mutation, EGFR-TKI treatment is not effective. The overall survival is short and the objective response rate is low. As for EGFR gene wild type patients with good performance status, besides EGFR-TKI treatment, other first generation cytotoxic drugs i.e. vinorelbine or ifosfamide maybe an alternative treatment. So the purpose of this clinical trial is to compare the effectiveness and safety of vinorelbine-ifosfamide with gefitinib in advanced or metastatic EGFR gene mutation negative NSCLC patients.
Non-small Cell Lung Cancer
Effects of Chemotherapy
Drug: Gefitinib group
Drug: Vinorelbine, Ifosfamide, Mesna
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase Ⅱ Randomized Clinical Trial Comparing Vinorelbine-ifosfamide With Gefitinib as Third-line Treatment in Advanced EGFR Gene Mutation Negative Non-small Cell Lung Cancer Patients|
- Progression free survival [ Time Frame: up to 52 weeks (about one year) ] [ Designated as safety issue: No ]From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks.
- Overall survival [ Time Frame: Up to 100 weeks ] [ Designated as safety issue: No ]From date of randomization until the date of death from any cause, assessed up to 100 weeks.
- objective response rate [ Time Frame: up to 9 weeks ] [ Designated as safety issue: No ]The objective response rate includes the complete remission and partial remission rate.
- the score of functional assessment of cancer treatment-lung (FACT-L) [ Time Frame: Up to 100 weeks ] [ Designated as safety issue: No ]FACL-L is assessed at different time points.(Date of randomization, 1 week after chemotherapy/EGFR-TKI, every cycle of chemotherapy/EGFR-TKI, every month of EGFR-TKI treatment/observation, up to 100 weeks)
- Number of participants with adverse events [ Time Frame: Up to six months ] [ Designated as safety issue: Yes ]The adverse events are assessed by National Cancer Institute-Common Toxicity Criteria (Version 3.0) (NCI-CTC).
|Study Start Date:||December 2012|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Gefitinib group Gefitinib (Iressa) 250mg once per day until progression disease or intolerant side effects
Drug: Gefitinib group
Gefitinib 250mg once per day until the progression disease or intolerant side effects
Other Name: Gefitinib (Iressa)
VI group Vinorelbine 25mg/m2 d1,d8;Ifosfamide 1.25g/m2 d1-d3(Usually Ifosfamide 2g d1-d3 with Mesna 400mg 0,4,8hours after Ifosfamide administration for 3 days);every 3 weeks;at least for 2-6 cycles depending on the progression disease or the patient's physical condition
Drug: Vinorelbine, Ifosfamide, Mesna
Vinorelbine 25mg/m2 d1,d8; Ifosfamide 1.25g/m1 d1-d3 (Usually 2g d1-d3); Mesna 400mg 0,4,8 hours after Ifosfamide administration for uroprotection d1-d3;
Other Name: VI group
Ifosfamide is a first generation cytotoxic drug to treat NSCLC. Phase Ⅱ studies demonstrated that single-agent ifosfamide administrated by various schedules produces response rates of 15-29%, with media survival times of 5-7 months. Ifosfamide has also been used in various combination regimens to treat NSCLC, including platinum based and non-platinum regimens. But in refractory NSCLC patients platinum and some third generation cytotoxic drugs have been used before. So in this study, ifosfamide is combined with vinorelbine. In previous study, Masters reported the objective response rate was 40% and the median survival duration was 50 weeks, with a 1-year survival rate of 48% with vinorelbine-ifosfamide regimen [Vinorelbine 15 mg/m2 on days 1-3, and ifosfamide 2.0g/m2 on days 1-3 with granulocyte-colony stimulating factor (G-CSF) support]. The dose limiting toxicity (DLT) of this regimen is myelosuppression. In our experience, the regimen of vinorelbine 25mg/m2 d1, d8 and ifosfamide 1.25g/m2 d1-d3 with Mesna uroprotection is safe in Chinese population and the objective response rate is about 7% (data not published).
Gefitinib is the first small molecule inhibitor that has directed activity towards EGFR and has shown appreciable response rates in phase Ⅱ trials of patients with previously treated advanced NSCLC. In the posterior analysis of Iressa Dose Evaluation in Advanced Lung Cancer (IDEAL) and IRESSA Survival Evaluation in Lung Cancer (ISEL) trials, the response rate with gefitinib ranges from 2.6% to 10% in wild-type EGFR gene NSCLC patients.
|Contact: Mengzhao Wang, MD||010-69155039 ext +firstname.lastname@example.org|
|Contact: Jing Zhao, MD||010-69158206 ext +email@example.com|
|Department of Respiratory Medicine, Peking Union Medical College Hospital||Recruiting|
|Beijing, Beijing, China, 100730|
|Contact: Mengzhao Wang, MD 010-69155039 ext +86 firstname.lastname@example.org|
|Contact: Jing Zhao, MD 010-69158206 ext +86 email@example.com|
|Sub-Investigator: Wei Zhong, MD|
|Sub-Investigator: Jinmei Luo, MD|
|Principal Investigator:||Mengzhao Wang, MD||Department of Respiratory Medicine, Peking Unoin Medical College Hospital|