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Gefitinib or Docetaxel as Second Line Therapy for Wild-type Epidermal Growth Factor Receptor (EGFR) NSCLC

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: NCT01755923
Recruitment Status : Unknown
Verified December 2012 by Peking Union Medical College Hospital.
Recruitment status was:  Recruiting
First Posted : December 24, 2012
Last Update Posted : December 24, 2012
Information provided by (Responsible Party):
Peking Union Medical College Hospital

Brief Summary:
Gefitinib, the first EGFR-tyrosine kinase inhibitor (TKI) in the world was examined as monotherapy in two phase Ⅱ studies called IDEAL trials. Response rate with doses of 250mg and 500mg/day were similar, ranging from 10% to 18%. Posterior analysis demonstrated that patients with EGFR mutation had an improved response rate (RR) to gefitinib compared to wild-type patients (46% versus 10%). The early trials that evaluated EGFR-TKIs for the second- and third-line settings of advanced NSCLC did not select patients on the basis of any EGFR marker. The IEESSA Survival Evaluation in Lung Cancer (ISEL) trial evaluated the role of second-line gefitinib 250mg/day in 1692 patients with advanced NSCLC. Patients with EGFR mutations had higher RR than patients without (37.5% versus 2.6%). From the above results, the response rate in patients without EGFR gene mutation was obviously different (10% versus 2.6%). The methods used for detecting EGFR gene mutation was different, which might contribute to the difference of response rates. In IDEAL trial, EGFR gene mutation was detected by sequencing. But in ISEL trial, EGFR gene mutation was detected by ARMS. As we know, ARMS was more sensitive than sequencing in detecting EGFR gene mutation. That is to say, in IDEAL trials some EGFR mutant patients were misdiagnosed as wild-type patients, so the response rate was higher. Recently, Wu Yi-Long et al reported that relative abundance of EGFR mutations predicted benefit form gefitinib treatment for advanced non small cell lung cancer. The study cohort was all Chinese. In this study, the objective response rate in patients without EGFR mutation detected by ARMS was 16.1%, which was significantly higher than the response rate of docetaxel. But in 2012 American society of clinical oncology (ASCO) annual meeting, the Tailor study in which Italian NSCLC patients were enrolled demonstrated a clear superiority of docetaxel over erlotinib as second line treatment for patients without EGFR mutations in exons 19 or 21. So we wonder if the racial difference is the determinant factor. So the purpose of this trial is to compare the efficacy and safety of gefitinib with docetaxel as second-line therapy for advanced or metastatic Chinese NSCLC patients with wild-type EGFR.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: Gefitinib Drug: Docetaxel Phase 2

Detailed Description:
The adoption of docetaxel as a standard second line therapy was based on data from two phase Ⅲ trials. In the first trail, docetaxel (75mg/m2, every 3 weeks) significantly prolonged median and 1-year survival duration compared with best supportive care (median survival, 7.5 months versus 4.6 months; P=0.010; 1-year survival, 37% versus 12%), although the response rate was low (5.5%). In the second study the 6-months and median survival rates were similar for docetaxel and vinorelbine or ifosfamide. However, the 1-year survival rate was significantly greater with docetaxel than ifosfamide or vinorelbine (32% versus 19%, P=0.025). In both studies docetaxel significantly improved some parameters of quality of life. Since these two pivotal studies, new potential second-line drugs were compared with the docetaxel standard of care. With regards to the therapeutic results of the docetaxel arm of these studies, it must be emphasized that response rates and survival data were highly and significantly reproducible.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ⅱ Randomized Controlled Trial to Compare Gefitinib With Docetaxel as Second-line Therapy for Advanced or Metastatic Non-squamous NSCLC Patients With Wild-type EGFR
Study Start Date : December 2012
Estimated Primary Completion Date : December 2013
Estimated Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Gefitinib
Gefitinib (Iressa) 250mg once per day until progression disease or intolerant side effects
Drug: Gefitinib
Gefitinib 250mg once per day until the progression disease or intolerant side effects
Other Name: Iressa

Active Comparator: Docetaxel
Docetaxel 75mg/m2,d1,every 3 weeks, at least 2-6 cycles depending on the progression disease or the patient's physical condition
Drug: Docetaxel
Docetaxel 75mg/m2 iv, d1,every 3 weeks, at least 2-6 cycles depending on the progression disease or the patient's physical condition
Other Name: Taxotere

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 the 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 ]
    FACT-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 6 months ]
    The adverse events are assessed by National Cancer Institute-Common Toxcity Criteria (Version 3.0)(NCI-CTC).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age more than 18 years old
  • Life expectancy more than 12 weeks
  • histologically or cytologically confirmed inoperable non-squamous 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
  • previous treatment include first-line platinum doublet chemotherapy
  • 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 and docetaxel
  • 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 of 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): NCT01755923

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

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China, Beijing
Department of Respiratory Medicine, Peking Union Medical College Hospita 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
Peking Union Medical College Hospital
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Principal Investigator: Mengzhao Wang, MD Peking Union Medical College Hospital
Publications of Results:

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Responsible Party: Peking Union Medical College Hospital Identifier: NCT01755923    
Other Study ID Numbers: PUMCH-S466
First Posted: December 24, 2012    Key Record Dates
Last Update Posted: December 24, 2012
Last Verified: December 2012
Keywords provided by Peking Union Medical College Hospital:
non-small cell lung cancer
wild-type EGFR
second-line therapy
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors