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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01749072
Recruitment Status : Unknown
Verified December 2012 by gwcmc.
Recruitment status was:  Recruiting
First Posted : December 13, 2012
Last Update Posted : December 13, 2012
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Effects of Chemotherapy Drug: Gefitinib group Drug: Vinorelbine, Ifosfamide, Mesna Phase 2

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  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : December 2012
Estimated Primary Completion Date : December 2016
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. objective response rate [ Time Frame: up to 9 weeks ]
    The objective response rate includes the complete remission and partial remission rate.

  3. 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)

  4. 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).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01749072

Contact: Mengzhao Wang, MD 010-69155039 ext +86
Contact: Jing Zhao, MD 010-69158206 ext +86

China, Beijing
Department of Respiratory Medicine, Peking Union Medical College Hospital Recruiting
Beijing, Beijing, China, 100730
Contact: Mengzhao Wang, MD    010-69155039 ext +86   
Contact: Jing Zhao, MD    010-69158206 ext +86   
Sub-Investigator: Wei Zhong, MD         
Sub-Investigator: Jinmei Luo, MD         
Sponsors and Collaborators
Principal Investigator: Mengzhao Wang, MD Department of Respiratory Medicine, Peking Unoin Medical College Hospital

Publications of Results:
Responsible Party: gwcmc Identifier: NCT01749072     History of Changes
Other Study ID Numbers: PUMCH-S464
First Posted: December 13, 2012    Key Record Dates
Last Update Posted: December 13, 2012
Last Verified: December 2012

Keywords provided by gwcmc:
non small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Isophosphamide mustard
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Alkylating
Alkylating Agents
Protective Agents
Physiological Effects of Drugs