Erlotinib Combined With Chemotherapy in TKI Resistant Non-Small Cell Lung Cancers

Hunan Province Tumor Hospital

Status and phase: Enrolling; Phase 2

Conditions: Carcinoma, Non-Small Cell Lung; EGFR Gene Mutation

Treatments: Drug: Gemcitabine platinum combined with erlotinib

Study type: Interventional

Funder types: Other

Identifiers

NCT02098954

TKIRR001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

experimental

Experimental group

Description:

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.

Treatment:

Drug: Gemcitabine platinum combined with erlotinib