Description:
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.
Title
- Brief Title: Erlotinib Combined With Chemotherapy in TKI Resistant Non-Small Cell Lung Cancers
- 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
Clinical Trial IDs
- ORG STUDY ID:
TKIRR001
- NCT ID:
NCT02098954
Conditions
- Carcinoma, Non-Small Cell Lung
- EGFR Gene Mutation
Interventions
| Drug | Synonyms | Arms |
|---|
| Gemcitabine platinum combined with erlotinib | Gemzar, Tarceva | experimental |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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. | - Gemcitabine platinum combined with erlotinib
|
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
| Maximum Eligible Age: | 75 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| 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 |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | mean overall survival(mOS) |
| Time Frame: | every 3 months up to 3 years, or until all the survival data is obtained |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | 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 |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Hunan Province Tumor Hospital |
Trial Keywords
- TKI
- resistance
- erlotinib
- combined chemotherapy
Last Updated
March 26, 2020
