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

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

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.

Study Overview

• Status: Unknown
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: combined group; Drug: Sequenced group

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mengzhao Wang, MD; Phone Number: 010-69155039; Email: mengzhaowang@sina.com
• Study Contact Backup: Name: Jing Zhao, MD; Phone Number: 010-69158206; Email: zhaojing0@163.com

Study Locations

• China
  • Beijing, China, 100730
    • Recruiting
    • Department of Respiratory Medicne, Peking Union Medical Hospital
    • Sub-Investigator: Wei Zhong, MD
    • Contact: Mengzhao Wang, MD; Phone Number: 010-69155039; Email: mengzhaowang@sina.com
    • Contact: Jing Zhao, MD; Phone Number: 010-69158206; Email: zhaojing0@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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: Pemetrexed (Alimta); Docetaxel (Taxotere); Gefitinib (Iressa)
Other: 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: Pemetrexed (Alimta); Docetaxel (Taxotere); Gefitinib (Iressa)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression free survival	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.	up to 52 weeks (about one year)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate	The objective response rate includes the complete remission and partial remission rate.	up to 9 weeks
overall survival	From date of randomization until the date of death from any cause, assessed up to 100 weeks.	up to 100 weeks
the score of functional assessment of cancer treatment-lung(FACT-L)	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)	up to 100weeks
Number of participants with adverse events	The adverse events are assessed by National Cancer Institute-Common Toxicity Criteria(version3.0) (NCI-CTC).	Participants will be followed for the duration of treatment, an expected average of 52 weeks.

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Mengzhao Wang, MD, Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Becker A, Crombag L, Heideman DA, Thunnissen FB, van Wijk AW, Postmus PE, Smit EF. Retreatment with erlotinib: Regain of TKI sensitivity following a drug holiday for patients with NSCLC who initially responded to EGFR-TKI treatment. Eur J Cancer. 2011 Nov;47(17):2603-6. doi: 10.1016/j.ejca.2011.06.046. Epub 2011 Jul 23.
• Oh IJ, Ban HJ, Kim KS, Kim YC. Retreatment of gefitinib in patients with non-small-cell lung cancer who previously controlled to gefitinib: a single-arm, open-label, phase II study. Lung Cancer. 2012 Jul;77(1):121-7. doi: 10.1016/j.lungcan.2012.01.012. Epub 2012 Feb 12.
• Li J, Hao X, Wang Y, Zhang X, Shi Y. [Clinical response to gefitinib retreatment of lung adenocarcinoma patients who benefited from an initial gefitinib therapy: a retrospective analysis]. Zhongguo Fei Ai Za Zhi. 2012 Jan;15(1):44-8. doi: 10.3779/j.issn.1009-3419.2012.01.09. Chinese.
• Watanabe S, Tanaka J, Ota T, Kondo R, Tanaka H, Kagamu H, Ichikawa K, Koshio J, Baba J, Miyabayashi T, Narita I, Yoshizawa H. Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis. BMC Cancer. 2011 Jan 1;11:1. doi: 10.1186/1471-2407-11-1.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Anticipated): October 1, 2015
• Study Completion (Anticipated): June 1, 2016

Study Registration Dates

• First Submitted: December 4, 2012
• First Submitted That Met QC Criteria: December 7, 2012
• First Posted (Estimate): December 10, 2012

Study Record Updates

• Last Update Posted (Estimate): December 10, 2012
• Last Update Submitted That Met QC Criteria: December 7, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: chemotherapy; non small cell lung cancer; retreatment; epidermal growth factor receptor tyrosine kinase inhibitor
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protein Kinase Inhibitors; Folic Acid Antagonists; Docetaxel; Gefitinib; Pemetrexed
• Other Study ID Numbers: PUMCH S-462