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

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ClinicalTrials.gov Identifier: NCT01749072
Recruitment Status : Unknown
Verified December 2012 by Peking Union Medical College Hospital.
Recruitment status was:  Recruiting
First Posted : December 13, 2012
Last Update Posted : December 13, 2012
Sponsor:
Information provided by (Responsible Party):
Peking Union Medical College Hospital

Tracking Information
First Submitted Date  ICMJE December 11, 2012
First Posted Date  ICMJE December 13, 2012
Last Update Posted Date December 13, 2012
Study Start Date  ICMJE December 2012
Estimated Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 12, 2012)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: December 12, 2012)
  • 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.
  • objective response rate [ Time Frame: 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) [ 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)
  • 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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vinorelbine-ifosfamide Versus Gefitinib for EGFR Gene Mutation Negative Non-small Cell Lung Cancer Patients
Official Title  ICMJE 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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-small Cell Lung Cancer
  • Effects of Chemotherapy
Intervention  ICMJE
  • Drug: Gefitinib group
    Gefitinib 250mg once per day until the progression disease or intolerant side effects
    Other Name: Gefitinib (Iressa)
  • 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
Study Arms  ICMJE
  • Gefitinib
    Gefitinib group Gefitinib (Iressa) 250mg once per day until progression disease or intolerant side effects
    Intervention: Drug: Gefitinib group
  • 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
    Intervention: Drug: Vinorelbine, Ifosfamide, Mesna
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: December 12, 2012)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2017
Estimated Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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;
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01749072
Other Study ID Numbers  ICMJE PUMCH-S464
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Peking Union Medical College Hospital
Study Sponsor  ICMJE Peking Union Medical College Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mengzhao Wang, MD Department of Respiratory Medicine, Peking Unoin Medical College Hospital
PRS Account Peking Union Medical College Hospital
Verification Date December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP