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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Peking Union Medical College Hospital
Sponsor:
Information provided by (Responsible Party):
Peking Union Medical College Hospital
ClinicalTrials.gov Identifier:
NCT01749072
First received: December 11, 2012
Last updated: December 12, 2012
Last verified: December 2012
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Peking Union Medical College Hospital:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: up to 52 weeks (about one year) ] [ Designated as safety issue: No ]
    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:
  • Overall survival [ Time Frame: Up to 100 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    The adverse events are assessed by National Cancer Institute-Common Toxicity Criteria (Version 3.0) (NCI-CTC).


Estimated Enrollment: 120
Study Start Date: December 2012
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Gefitinib
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)
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
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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;
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01749072

Contacts
Contact: Mengzhao Wang, MD 010-69155039 ext +86 mengzhaowang@sina.com
Contact: Jing Zhao, MD 010-69158206 ext +86 pumchzj@sina.com

Locations
China, Beijing
Department of Respiratory Medicine, Peking Union Medical College Hospital Recruiting
Beijing, Beijing, China, 100730
Contact: Mengzhao Wang, MD    010-69155039 ext +86    mengzhaowang@sina.com   
Contact: Jing Zhao, MD    010-69158206 ext +86    pumchzj@sina.com   
Sub-Investigator: Wei Zhong, MD         
Sub-Investigator: Jinmei Luo, MD         
Sponsors and Collaborators
Peking Union Medical College Hospital
Investigators
Principal Investigator: Mengzhao Wang, MD Department of Respiratory Medicine, Peking Unoin Medical College Hospital
  More Information

Publications:
Responsible Party: Peking Union Medical College Hospital
ClinicalTrials.gov Identifier: NCT01749072     History of Changes
Other Study ID Numbers: PUMCH-S464
Study First Received: December 11, 2012
Last Updated: December 12, 2012
Health Authority: China: Food and Drug Administration

Keywords provided by Peking Union Medical College Hospital:
non small cell lung cancer
chemotherapy
gefitinib
vinorelbine
ifosfamide

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

ClinicalTrials.gov processed this record on August 28, 2014