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

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:
NCT01755923
First received: December 17, 2012
Last updated: December 19, 2012
Last verified: December 2012
  Purpose

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 Intervention Phase
Non-small Cell Lung Cancer
Drug: Gefitinib
Drug: Docetaxel
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 Controlled Trial to Compare Gefitinib With Docetaxel as Second-line Therapy for Advanced or Metastatic Non-squamous NSCLC Patients With Wild-type EGFR

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 the 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 ]
    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)

  • Number of participants with adverse events [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]
    The adverse events are assessed by National Cancer Institute-Common Toxcity Criteria (Version 3.0)(NCI-CTC).


Estimated Enrollment: 60
Study Start Date: December 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01755923

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 Hospita 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 Peking Union Medical College Hospital
  More Information

Publications:

Responsible Party: Peking Union Medical College Hospital
ClinicalTrials.gov Identifier: NCT01755923     History of Changes
Other Study ID Numbers: PUMCH-S466
Study First Received: December 17, 2012
Last Updated: December 19, 2012
Health Authority: China: Food and Drug Administration

Keywords provided by Peking Union Medical College Hospital:
non-small cell lung cancer
wild-type EGFR
gefitinib
docetaxel
second-line therapy

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
Docetaxel
Gefitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2014