Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Vinorelbine

Ifosfamide

Isophosphamide mustard

Gefitinib

Mesna

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Gefitinib group Gefitinib (Iressa) 250mg once per day until progression disease or intolerant side effects

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

Gefitinib 250mg once per day until the progression disease or intolerant side effects

Gefitinib group

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;

Vinorelbine, Ifosfamide, Mesna

Mengzhao Wang, MD

Jing Zhao, MD

Wei Zhong, MD

Jinmei Luo, MD

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.

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.

Vinorelbine-ifosfamide Versus Gefitinib for EGFR Gene Mutation Negative Non-small Cell Lung Cancer Patients

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

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.

From date of randomization until the date of death from any cause, assessed up to 100 weeks.

The objective response rate includes the complete remission and partial remission rate.

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)

The adverse events are assessed by National Cancer Institute-Common Toxicity Criteria (Version 3.0) (NCI-CTC).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Vinorelbine-ifosfamide Versus Gefitinib for EGFR Gene Mutation Negative Non-small Cell Lung Cancer Patients	NCT01749072	Non-small Cell ... Effects of Chem...	Gefitinib group Vinorelbine, If...	18 Years - 70 Years	Peking Union Medical College Hospital
Vinorelbine-ifosfamide Versus Gefitinib for EGFR Gene Mutation Negative Non-small Cell Lung Cancer Patients	NCT01749072	Non-small Cell ... Effects of Chem...	Gefitinib group Vinorelbine, If...	18 Years - 70 Years	Peking Union Medical College Hospital

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