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

Phase 2

• Conditions: Non-small Cell Lung Cancer; Effects of Chemotherapy
• Interventions: Drug: Gefitinib group; Drug: Vinorelbine, Ifosfamide, Mesna

• Registration Number: NCT01749072
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

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.

Detailed 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.

Study Timeline

• Status Verified: 2012-12
• Study Start: 2012-12
• Study First Submitted: 2012-12-11
• Study First Submitted QC: 2012-12-12
• Last Update Submitted: 2012-12-12
• Study First Posted: 2012-12-13
• Last Update Posted: 2012-12-13
• Primary Completion: 2016-12
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Gefitinib	Gefitinib group	Gefitinib group Gefitinib (Iressa) 250mg once per day until progression disease or intolerant side effects
Vinorelbine-Ifosfamide	Vinorelbine, Ifosfamide, Mesna	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

Primary Outcome Measures

Name	Time	Method
Progression free survival	up to 52 weeks (about one year)	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.

Secondary Outcome Measures

Name	Time	Method
Overall survival	Up to 100 weeks	From date of randomization until the date of death from any cause, assessed up to 100 weeks.
objective response rate	up to 9 weeks	The objective response rate includes the complete remission and partial remission rate.
the score of functional assessment of cancer treatment-lung (FACT-L)	Up to 100 weeks	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	Up to six months	The adverse events are assessed by National Cancer Institute-Common Toxicity Criteria (Version 3.0) (NCI-CTC).

Trial Locations

Locations (1)

Department of Respiratory Medicine, Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China