Carcinoma, Non-Small Cell LungPhase 2NCT02098954
Erlotinib Combined With Chemotherapy in TKI Resistant Non-Small Cell Lung Cancers
A Phase 2 study testing Gemcitabine platinum combined with erlotinib in people with Carcinoma, Non-Small Cell Lung and EGFR Gene Mutation, run by Hunan Province Tumor Hospital at 1 site in China.
Trial summary
Numerous evidences verified that erlotinib could dramatically improve the PFS and OS of non-small cell lung cancers who harbor EGFR sensitive mutations, however, primary or secondary resistance will be developed after TKI treatment, doctors do plenty of researches to overcome TKI resistance. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Carcinoma, Non-Small Cell Lung, EGFR Gene Mutation
- What is being tested?
- Gemcitabine platinum combined with erlotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2014to 12 Dec 2025
- 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
- advanced non-small cell lung cancer, stage IIIB/IV
- non-squamous
- EGFR sensitive mutations, such as exon 19 del, or exon 21 L858R
- received first line TKIs treatment and developed TKI resistance
- ECOG 0-2
Who cannot join
- squamous non-small cell lung cancer
- patients have unstable brain metastasis, predict survival less than 8 weeks
- spinal-cord compression without evidence of stabilisation or treatment
- women who were pregnant or lactating; women with a positive or no available pregnancy test result at baseline
- patients have any unstable illness that could not receive further treatment
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Hunan Province Tumor Hospital
Changsha, Hunan
Nong Yang, MD, +86 731 89762323, yangnong0217@163.com
Ming Zhou, MD, +86 731 89762321, zhouming243@gmail.com
About this study
Official title: Second Line Erlitinib Combination With Gemcitabine Cisplatinum in Non-small Cell Lung Cancer Patients Who Harbored EGFR Sensitive Mutation Developed Resistance After First Line TKI Treatment
Numerous evidences verified that erlotinib could dramatically improve the PFS and OS of non-small cell lung cancers who harbor EGFR sensitive mutations, however, primary or secondary resistance will be developed after TKI treatment, doctors do plenty of researches to overcome TKI resistance. FAST ACT-2 study present that, first line erlotinib combined with chemotherapy could improved mOS to more than 30 months in NSCLCs who harbor EGFR sensitive mutations, several study shows that sensitive mutations still exist after TKI resistance, because of the next generation TKIs(such as BIBW2992) are not avaliable at present, agents for met amplification(such as Crizotinib) are so expensive that many Chinese patients could not support. Thus, the investigators hypothesis that, after first line TKI treatment, the patients who developed TKI resistance could still benefit from second line TKI combined with chemotherapy.
Read the detailed description
The investigators will enroll patients diagnosed with advanced non-squamous,non-small cell lung cancer, patients with EGFR TKI sensitive mutations and developed TKI resistance in first line treatment. After enrollment, the investigators will do biopsy again before second line treatment to find out the potential mechanism of TKI resistance, do EGFR mutation test for both sensitive and resistant mutation in exon 18, 19, 20 and 21; do KRAS, BRAF and PI3K mutation test, do FISH for MET and HER-2, the investigators do all these test to evaluated both primary and secondary resistance, the investigators do all these tests to get an overview for EGFR mutation status of each patient who develop TKI resistance. For second line treatment, patients will received a 28 days gemcitabine platinum combined with erlotinib scheme, after 4 cycle of combined chemotherapy, patients will receive erlotinib for further treatment until progression disease. For the patients who have stable brain metastases, combined chemotherapy should begin after local treatment, such as whole brain radiotherapy or sterotactic radiosurgery.
the main endpoint of this study is mean PFS, second endpoints of this study consist of mean OS, 8 week ORR.
- Conditions
- Carcinoma, Non-Small Cell Lung, EGFR Gene Mutation
- Being tested
- Gemcitabine platinum combined with erlotinib
- Keywords
- TKI, resistance, erlotinib, combined chemotherapy
- 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.
Gemcitabine platinum combined with erlotinibDrug
Also called Gemzar, Tarceva
patients will received a 28 days gemcitabine platinum combined with erlotinib scheme, after 4 cycles combined chemotherapy, patients will receive erlotinib for maintain treatment until progression disease.Gemcitabine for day 1 and day 8, 1250mg/m2. Platinum for day 1, 75mg/m2. Erlotinib for day 9-21 during combined chemotherapy, 150mg/day, then erlotinib should be used daily until patients develop progression disease.
| Study group | Role | What they receive |
|---|---|---|
| experimental | Experimental | patients will received a 28 days gemcitabine platinum combined with erlotinib scheme(gemcitabine for day 1 and day 8, 1250mg/m2. Platinum for day 1, 75mg/m2. Erlotinib for 150mg/day, day 9-21 every cycle, after 4 cycles, erlotinib should be used daily), after 4 cycle of combined chemotherapy, patients will receive erlotinib for further treatment until progression disease. Receives: Drug: Gemcitabine platinum combined with erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
mean progression free survival(mPFS)
mean progression free survival(mPFS) will be recorded in enroll patients who received second line gemcitabine platinum combined with erlotinib. mPFS should be measured before second line treatment, before the third combined chemotherapy, after the fourth combined chemotherapy, every 3 months during erlotinib treatment, mPFS should be measured up to two years or every time progression disease occurs within two years.
Measured: after patients receive treatment, mPFS should be measured before the third cycle of chemotherapy, after the fourth cycle, mPFS should be measured every 3 months up to two years
Secondary outcomes (2)
mean overall survival(mOS)
mOS should be measured since enrollment, every 3 months we will contact patients to find out detail survival data of each patient until 3 years, or within 3 years if all survival data is obtained.
Measured: every 3 months up to 3 years, or until all the survival data is obtained
8 week overall response rate(8 week ORR)
8 week ORR should be measured after enrollment, after combined chemotherapy for 8 weeks, the exact time point should be the ninth week during combined chemotherapy. CR, PR, SD shoud be measured according to RESICT 1.1
Measured: 8 week ORR should be measured after enrollment, the exact time point should be the ninth week after combined chemotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2014 (estimated)
- Study start1 Jul 2014
- Primary completion1 Dec 2024 (estimated)
- Study completion12 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Non-Small Cell LungStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hunan Province Tumor Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yongchang Zhang, Hunan Province Tumor Hospital
- Investigators
- Nong Yang, MD, Study chair, Hunan Province Tumor Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02098954
- Sponsor's protocol ID
- TKIRR001
- Status last verified
- Dec 2023
- First submitted
- 20 Mar 2014
- Last updated
- 27 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Wu YL, Lee JS, Thongprasert S, Yu CJ, Zhang L, Ladrera G, Srimuninnimit V, Sriuranpong V, Sandoval-Tan J, Zhu Y, Liao M, Zhou C, Pan H, Lee V, Chen YM, Sun Y, Margono B, Fuerte F, Chang GC, Seetalarom K, Wang J, Cheng A, Syahruddin E, Qian X, Ho J, Kurnianda J, Liu HE, Jin K, Truman M, Bara I, Mok T. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol. 2013 Jul;14(8):777-86. doi: 10.1016/S1470-2045(13)70254-7. Epub 2013 Jun 17.
PubMed 23782814Suda K, Mizuuchi H, Maehara Y, Mitsudomi T. Acquired resistance mechanisms to tyrosine kinase inhibitors in lung cancer with activating epidermal growth factor receptor mutation--diversity, ductility, and destiny. Cancer Metastasis Rev. 2012 Dec;31(3-4):807-14. doi: 10.1007/s10555-012-9391-7.
PubMed 22736441
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Second Line Erlitinib Combination With Gemcitabine Cisplatinum in Non-small Cell Lung Cancer Patients Who Harbored EGFR Sensitive Mutation Developed Resistance After First Line TKI Treatment
- ClinicalTrials.gov ID
- NCT02098954
- Acronym / sponsor ID
- TKIRR001
- Conditions
- Carcinoma, Non-Small Cell Lung, EGFR Gene Mutation
- Keywords
- TKI, resistance, erlotinib, combined chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Hunan Province Tumor HospitalUniversity, hospital or other
- Study start
- 1 Jul 2014 (actual)
- Primary completion
- 1 Dec 2024 (estimated)
- Study completion
- 12 Dec 2025 (estimated)
- First posted
- 28 Mar 2014 (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.
Numerous evidences verified that erlotinib could dramatically improve the PFS and OS of non-small cell lung cancers who harbor EGFR sensitive mutations, however, primary or secondary resistance will be developed after TKI treatment, doctors do plenty of researches to overcome TKI resistance. FAST ACT-2 study present that, first line erlotinib combined with chemotherapy could improved mOS to more than 30 months in NSCLCs who harbor EGFR sensitive mutations, several study shows that sensitive mutations still exist after TKI resistance, because of the next generation TKIs(such as BIBW2992) are not avaliable at present, agents for met amplification(such as Crizotinib) are so expensive that many Chinese patients could not support. Thus, the investigators hypothesis that, after first line TKI treatment, the patients who developed TKI resistance could still benefit from second line TKI combined with chemotherapy.
Detailed description
The investigators will enroll patients diagnosed with advanced non-squamous,non-small cell lung cancer, patients with EGFR TKI sensitive mutations and developed TKI resistance in first line treatment. After enrollment, the investigators will do biopsy again before second line treatment to find out the potential mechanism of TKI resistance, do EGFR mutation test for both sensitive and resistant mutation in exon 18, 19, 20 and 21; do KRAS, BRAF and PI3K mutation test, do FISH for MET and HER-2, the investigators do all these test to evaluated both primary and secondary resistance, the investigators do all these tests to get an overview for EGFR mutation status of each patient who develop TKI resistance. For second line treatment, patients will received a 28 days gemcitabine platinum combined with erlotinib scheme, after 4 cycle of combined chemotherapy, patients will receive erlotinib for further treatment until progression disease. For the patients who have stable brain metastases, combined chemotherapy should begin after local treatment, such as whole brain radiotherapy or sterotactic radiosurgery.
the main endpoint of this study is mean PFS, second endpoints of this study consist of mean OS, 8 week ORR.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| experimental | Experimental | Drug: Gemcitabine platinum combined with erlotinibpatients will received a 28 days gemcitabine platinum combined with erlotinib scheme(gemcitabine for day 1 and day 8, 1250mg/m2. Platinum for day 1, 75mg/m2. Erlotinib for 150mg/day, day 9-21 every cycle, after 4 cycles, erlotinib should be used daily), after 4 cycle of combined chemotherapy, patients will receive erlotinib for further treatment until progression disease. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- advanced non-small cell lung cancer, stage IIIB/IV
- non-squamous
- EGFR sensitive mutations, such as exon 19 del, or exon 21 L858R
- received first line TKIs treatment and developed TKI resistance
- ECOG 0-2
Key exclusion criteria (5 listed)
- squamous non-small cell lung cancer
- patients have unstable brain metastasis, predict survival less than 8 weeks
- spinal-cord compression without evidence of stabilisation or treatment
- women who were pregnant or lactating; women with a positive or no available pregnancy test result at baseline
- patients have any unstable illness that could not receive further treatment
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 |
|---|---|---|
| Gemcitabine platinum combined with erlotinibAlso: Gemzar, Tarcevapatients will received a 28 days gemcitabine platinum combined with erlotinib scheme, after 4 cycles combined chemotherapy, patients will receive erlotinib for maintain treatment until progression disease.Gemcitabine for day 1 and day 8, 1250mg/m2. Platinum for day 1, 75mg/m2. Erlotinib for day 9-21 during combined chemotherapy, 150mg/day, then erlotinib should be used daily until patients develop progression disease. | Drug | experimental |
Primary outcome
mean progression free survival(mPFS)
Time frame: after patients receive treatment, mPFS should be measured before the third cycle of chemotherapy, after the fourth cycle, mPFS should be measured every 3 months up to two years
mean progression free survival(mPFS) will be recorded in enroll patients who received second line gemcitabine platinum combined with erlotinib. mPFS should be measured before second line treatment, before the third combined chemotherapy, after the fourth combined chemotherapy, every 3 months during erlotinib treatment, mPFS should be measured up to two years or every time progression disease occurs within two years.
2 secondary outcomes
mean overall survival(mOS)
Time frame: every 3 months up to 3 years, or until all the survival data is obtained
8 week overall response rate(8 week ORR)
Time frame: 8 week ORR should be measured after enrollment, the exact time point should be the ninth week after combined chemotherapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2023.
- Results publication: PubMed 23782814Wu YL, Lee JS, Thongprasert S, Yu CJ, Zhang L, Ladrera G, Srimuninnimit V, Sriuranpong V, Sandoval-Tan J, Zhu Y, Liao M, Zhou C, Pan H, Lee V, Chen YM, Sun Y, Margono B, Fuerte F, Chang GC, Seetalarom K, Wang J, Cheng A, Syahruddin E, Qian X, Ho J, Kurnianda J, Liu HE, Jin K, Truman M, Bara I, Mok T. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol. 2013 Jul;14(8):777-86. doi: 10.1016/S1470-2045(13)70254-7. Epub 2013 Jun 17.
- Results publication: PubMed 22736441Suda K, Mizuuchi H, Maehara Y, Mitsudomi T. Acquired resistance mechanisms to tyrosine kinase inhibitors in lung cancer with activating epidermal growth factor receptor mutation--diversity, ductility, and destiny. Cancer Metastasis Rev. 2012 Dec;31(3-4):807-14. doi: 10.1007/s10555-012-9391-7.
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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.
Nong Yang, MD study chair
Hunan Province Tumor 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 Gemcitabine platinum combined with erlotinib in people with Carcinoma, Non-Small Cell Lung and EGFR Gene Mutation, run by Hunan Province Tumor 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 5 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 27 Dec 2023. 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 Nong Yang, MD (+86 731 89762323, yangnong0217@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
mean progression free survival(mPFS) (time frame: after patients receive treatment, mPFS should be measured before the third cycle of chemotherapy, after the fourth cycle, mPFS should be measured every 3 months up to two years). 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 NCT02098954, which also lists 2 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 27 Dec 2023.