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

December 12, 2012 updated by: Peking Union Medical College Hospital

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

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.

Study Overview

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 Type

Interventional

Enrollment (Anticipated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Beijing
      • Beijing, Beijing, China, 100730
        • Recruiting
        • Department of Respiratory Medicine, Peking Union Medical College Hospital
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Wei Zhong, MD
        • Sub-Investigator:
          • Jinmei Luo, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Gefitinib
Gefitinib group Gefitinib (Iressa) 250mg once per day until progression disease or intolerant side effects
Gefitinib 250mg once per day until the progression disease or intolerant side effects
Other Names:
  • Gefitinib (Iressa)
Other: Vinorelbine-Ifosfamide
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
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 Names:
  • VI group

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: 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.
up to 52 weeks (about one year)

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Mengzhao Wang, MD, Department of Respiratory Medicine, Peking Unoin Medical College Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2012

Primary Completion (Anticipated)

December 1, 2016

Study Completion (Anticipated)

December 1, 2017

Study Registration Dates

First Submitted

December 11, 2012

First Submitted That Met QC Criteria

December 12, 2012

First Posted (Estimate)

December 13, 2012

Study Record Updates

Last Update Posted (Estimate)

December 13, 2012

Last Update Submitted That Met QC Criteria

December 12, 2012

Last Verified

December 1, 2012

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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