Non Small Cell Lung CancerPhase 2NCT01746277
Study of Chemotherapy Sequenced by or Combined With EGFR-TKIs for NSCLC Patients Failed to EGFR-TKIs Therapy
A Phase 2 study testing combined group and Sequenced group in people with Non Small Cell Lung Cancer, run by Peking Union Medical College Hospital at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- combined group and Sequenced group
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- Oct 2012to Jun 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- Eastern cooperative oncology group performance status (ECOG PS) ≤ 2
- life expectancy ≥ 12 weeks
- adequate hematological, renal, and hepatic functions
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Respiratory Medicne, Peking Union Medical Hospital
Beijing, 100730
Mengzhao Wang, MD, 010-69155039, mengzhaowang@sina.com
Jing Zhao, MD, 010-69158206, zhaojing0@163.com
About this study
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
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.
Read the 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.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- combined group, Sequenced group
- Keywords
- non small cell lung cancer, chemotherapy, epidermal growth factor receptor tyrosine kinase inhibitor, retreatment
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
combined groupDrug
Also called Docetaxel (Taxotere), Pemetrexed (Alimta), Gefitinib (Iressa)
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 groupDrug
Also called Docetaxel (Taxotere), Pemetrexed (Alimta), Gefitinib (Iressa)
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.
| Study group | Role | What they receive |
|---|---|---|
| combined group | Other | 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. Receives: Drug: combined group |
| sequenced group | Other | 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. Receives: Drug: Sequenced group |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 52 weeks (about one year)
Secondary outcomes (4)
overall survival
From date of randomization until the date of death from any cause, assessed up to 100 weeks.
Measured: up to 100 weeks
objective response rate
The objective response rate includes the complete remission and partial remission rate.
Measured: up to 9 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)
Measured: 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).
Measured: Participants will be followed for the duration of treatment, an expected average of 52 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2012 (estimated)
- Study startOct 2012
- Primary completionOct 2015 (estimated)
- Study completionJun 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mengzhao Wang, MD, Principal investigator, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01746277
- Sponsor's protocol ID
- PUMCH S-462
- Status last verified
- Dec 2012
- First submitted
- 4 Dec 2012
- Last updated
- 10 Dec 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 22333554Li 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.
PubMed 22237124Watanabe 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.
PubMed 21194487Becker 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.
PubMed 21784628
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01746277
- Acronym / sponsor ID
- PUMCH S-462
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- non small cell lung cancer, chemotherapy, epidermal growth factor receptor tyrosine kinase inhibitor, retreatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Oct 2015 (estimated)
- Study completion
- Jun 2016 (estimated)
- First posted
- 10 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| combined group | Other | Drug: combined groupcombined 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. |
| sequenced group | Other | Drug: Sequenced groupsequenced 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| combined groupAlso: Docetaxel (Taxotere), Pemetrexed (Alimta), Gefitinib (Iressa)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 |
| Sequenced groupAlso: Docetaxel (Taxotere), Pemetrexed (Alimta), Gefitinib (Iressa)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 |
Primary outcome
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.
4 secondary outcomes
overall survival
Time frame: up to 100 weeks
objective response rate
Time frame: up to 9 weeks
the score of functional assessment of cancer treatment-lung(FACT-L)
Time frame: up to 100weeks
Number of participants with adverse events
Time frame: Participants will be followed for the duration of treatment, an expected average of 52 weeks.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2012.
- Results publication: PubMed 22333554Oh 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.
- Results publication: PubMed 22237124Li 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.
- Results publication: PubMed 21194487Watanabe 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.
- Results publication: PubMed 21784628Becker 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mengzhao Wang, MD principal investigator
Peking Union Medical College Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing combined group and Sequenced group in people with Non Small Cell Lung Cancer, run by Peking Union Medical College Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mengzhao Wang, MD (010-69155039, mengzhaowang@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
progression free survival (time frame: up to 52 weeks (about one year)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01746277, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2012.