Study of Chemotherapy Sequenced by or Combined With EGFR-TKIs for NSCLC Patients Failed to EGFR-TKIs Therapy

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:
NCT01746277
First received: December 4, 2012
Last updated: December 7, 2012
Last verified: December 2012
  Purpose

There are two different treatment modes for NSCLC patients who failed to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) after initially responding to EGFR-TKI. One is EGFR-TKI combined with chemotherapy and the other is chemotherapy followed by EGFR-TKI. It is unclear which one is more suitable to this group of lung cancer patients. So this phase Ⅱclinical trial is designed to compare the efficiency and safety of these two different treatment modes.


Condition Intervention Phase
Non Small Cell Lung Cancer
Drug: combined group
Drug: Sequenced group
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 Chemotherapy Sequenced by EGFR-TKIs and Chemotherapy Combined With EGFR-TKIs for Advanced or Metastatic NSCLC Patients Failed to EGFR-TKIs Therapy

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 100weeks ] [ Designated as safety issue: No ]
    FACL-L is assessed at different time points.(Date of randomization,1 week after chemotherapy,every cycle of chemotherapy,every month of EGFR-TKI maintain treatment,up to 100 weeks)

  • Number of participants with adverse events [ Time Frame: Participants will be followed for the duration of treatment, an expected average of 52 weeks. ] [ Designated as safety issue: Yes ]
    The adverse events are assessed by National Cancer Institute-Common Toxicity Criteria(version3.0) (NCI-CTC).


Estimated Enrollment: 60
Study Start Date: October 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
combined group
combined group chemotherapy with docetaxel 75mg/m2 d1 or pemetrexed 500mg/m2 d1, every 3 weeks,at least 2 cycles and the maximal cycle is 6 depending on disease evaluation and patient's physical condition combined with gefitinib 250mg once per day from the start day of chemotherapy until disease progression or intolerable side effects.
Drug: combined group
chemotherapy with docetaxel 75mg/m2 d1 or pemetrexed 500mg/m2 d1, every 3 weeks,at least 2 cycles and the maximal cycle is 6 depending on disease evaluation and patient's physical condition combined with gefitinib 250mg once per day from the start day of chemotherapy until disease progression or intolerable side effects.
Other Names:
  • Docetaxel (Taxotere)
  • Pemetrexed (Alimta)
  • Gefitinib (Iressa)
sequenced group
sequenced group chemotherapy with docetaxel 75mg/m2 d1 or pemetrexed 500mg/m2 d1, every 3 weeks,at least 2 cycles and the maximal cycles is 6 depending on disease evaluation or patient's physical condition sequenced by gefitinib 250mg once per day until disease progression or intolerable side effects.
Drug: Sequenced group
sequenced group chemotherapy with docetaxel 75mg/m2 d1 or pemetrexed 500mg/m2 d1, every 3 weeks,at least 2 cycles and the maximal cycles is 6 depending on disease evaluation or patient's physical condition sequenced by gefitinib 250mg once per day until disease progression or intolerable side effects.
Other Names:
  • Docetaxel (Taxotere)
  • Pemetrexed (Alimta)
  • Gefitinib (Iressa)

Detailed Description:

Responses to EGFR-TKIs are quiet dramatic and durable, especially in patients with EGFR gene classic mutations, such as 19 deletion or 21 leucine 858 arginine(L858R). However, most patients with NSCLC who respond to EGFR-TKIs eventually experience progression of disease after approximately 12 months. The lack of an established therapeutic option for NSCLC patients who have progressive disease after EGFR-TKIs failure poses a great challenge to physicians in terms of how best to manage this growing group of lung cancer patients.

In clinical practice some of the initially EGFR-TKI sensitive tumors which progressed evidence a striking increase in tumor volume within several weeks, after being taken off EGFR-TKI. This response is called "rebound phenomenon". Most experts still believe that these tumors continue to be "oncogene-addicted" to EGFR. So it is rational that EGFR-TKI combined with another chemotherapy regimen can be used to treat NSCLC after the failure of EGFR-TKI therapy.

However in some phase Ⅱclinical trials involved a few NSCLC patients who failed to EGFR-TKI therapy, another treatment mode, that is to say, at least one cytotoxic chemotherapy was used firstly then switched to EGFR-TKI therapy until progression of disease, was used and called reintroduction or retreatment of EGFR-TKI. Using this treatment mode, some investigators reported the partial remission (PR) and disease control rate (DCR) were observed in 21.7%-36% and 65.2%-86% NSCLC patients.

  Eligibility

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

Inclusion Criteria:

  • age ≥ 18 years
  • histologically and cytologically proven non-small cell bronchogenic carcinoma (sputum cytology alone was not acceptable)
  • clinical stages ⅢB or Ⅳ
  • recurrent or refractory disease following previous first-line chemotherapy regimens containing platinum and second-line EGFR-TKIs therapy
  • partial remission (PR) or stable disease (SD) at least for 6 months during previous EGFR-TKI treatment
  • at least one bidimensionally measurable or radiographically assessable lesion
  • Eastern cooperative oncology group performance status (ECOG PS) ≤ 2
  • life expectancy ≥ 12 weeks
  • adequate hematological, renal, and hepatic functions

Exclusion Criteria:

  • 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: NCT01746277

Contacts
Contact: Mengzhao Wang, MD 010-69155039 mengzhaowang@sina.com
Contact: Jing Zhao, MD 010-69158206 zhaojing0@163.com

Locations
China
Department of Respiratory Medicne, Peking Union Medical Hospital Recruiting
Beijing, China, 100730
Contact: Mengzhao Wang, MD    010-69155039    mengzhaowang@sina.com   
Contact: Jing Zhao, MD    010-69158206    zhaojing0@163.com   
Sub-Investigator: Wei Zhong, 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: NCT01746277     History of Changes
Other Study ID Numbers: PUMCH S-462
Study First Received: December 4, 2012
Last Updated: December 7, 2012
Health Authority: China: Food and Drug Administration

Keywords provided by Peking Union Medical College Hospital:
non small cell lung cancer
chemotherapy
epidermal growth factor receptor tyrosine kinase inhibitor
retreatment

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Docetaxel
Pemetrexed
Gefitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Enzyme Inhibitors
Folic Acid Antagonists
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014