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

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Unknown; Phase 2

Conditions: Non-small Cell Lung Cancer; Effects of Chemotherapy

Treatments: Drug: Gefitinib group; Drug: Vinorelbine, Ifosfamide, Mesna

Study type: Interventional

Funder types: Other

Identifiers

NCT01749072

PUMCH-S464

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• age range:18-70 years old
• life expectancy more than 12 weeks
• histologically or cytologically confirmed inoperable NSCLC (stage ⅢB/Ⅳ)
• ineligible for curative radiotherapy
• no prior radiotherapy for the target lesions
• Eastern Cooperative Oncology Group (ECOG) performance score of 0-2;
• prior treatments include first-line platinum doublet chemotherapy i.e. PC or GP and second-line chemotherapy with docetaxel or pemetrexed;
• No EGFR gene mutation detected by Scorpions-ARMS;
• at least one bidimensionally measurable or radiographically assessable lesion;
• adequate bone marrow reserve;
• adequate hepatic and renal function;

Exclusion criteria

• prior treatments including any of the following drugs:gefitinib,vinorelbine and ifosfamide;
• additional malignancies;
• uncontrolled systemic disease;
• any evidence of clinically active interstitial lung disease;
• newly diagnosed central nervous system (CNS) metastasis and not treated by radiotherapy or surgery;
• pregnancy or breast feeding phase;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 2 patient groups

Gefitinib

Other group

Description:

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

Treatment:

Drug: Gefitinib group

Vinorelbine-Ifosfamide

Other group

Description:

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

Treatment:

Drug: Vinorelbine, Ifosfamide, Mesna