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

NCT ID: NCT01746277

Last Updated: 2012-12-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-10-31

Study Completion Date

2016-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Non Small Cell Lung Cancer

Keywords

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non small cell lung cancer chemotherapy epidermal growth factor receptor tyrosine kinase inhibitor retreatment

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type OTHER

combined group

Intervention Type DRUG

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.

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.

Group Type OTHER

Sequenced group

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Docetaxel (Taxotere) Pemetrexed (Alimta) Gefitinib (Iressa) Docetaxel (Taxotere) Pemetrexed (Alimta) Gefitinib (Iressa)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Peking Union Medical College Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mengzhao Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Peking Union Medical College Hospital

Locations

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Department of Respiratory Medicne, Peking Union Medical Hospital

Beijing, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Mengzhao Wang, MD

Role: CONTACT

Phone: 010-69155039

Email: [email protected]

Jing Zhao, MD

Role: CONTACT

Phone: 010-69158206

Email: [email protected]

Facility Contacts

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Mengzhao Wang, MD

Role: primary

Jing Zhao, MD

Role: backup

References

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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.

Reference Type RESULT
PMID: 22333554 (View on PubMed)

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.

Reference Type RESULT
PMID: 22237124 (View on PubMed)

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.

Reference Type RESULT
PMID: 21194487 (View on PubMed)

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.

Reference Type RESULT
PMID: 21784628 (View on PubMed)

Other Identifiers

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PUMCH S-462

Identifier Type: -

Identifier Source: org_study_id