EGFR Mutation, Lung Adenocarcinoma
Conditions
Keywords
Lung Adenocarcinoma, EGFR mutation, Gefitinib, Berberine
Brief summary
Rationale: Advanced non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations (del19 or L858R) show an impressive progression-free survival between 9 and 11 months when treated with gefitinib. Combination of gefitinib and berberine could improve efficacy in lung cancer with EGFR mutation in vivo and vitro. The investigators hypothesize that progression-free survival could be improved by combination of gefitinib and berberine.
Detailed description
Strong lipogenic activity and high expression of sterol regulatory element-binding protein 1 (SREBP-1) were found in gefitinib-resistance NSCLC cells. Berberine, an effective suppressor of SREBP1 and lipogenesis regulated through ROS/AMPK pathway, selectively inhibited the growth of gefitinib-resistance NSCLC cells but not that of normal cells. It effectively caused mitochondrial dysfunction, activated reactive oxygen species (ROS)/AMPK pathway and finally suppressed cellular lipogenesis and cell proliferation. Addition of ROS blocker, AMPK inhibitor and palmitic acid significantly reduced the effect of Berberine. In in vivo study, treatment of Berberine led to significant inhibition of mouse tumor xenograft growth.
Interventions
DRUGgefitinib
Patients will be treated with gefitinib, 250 mg p.o., daily
DRUGBerberine
Patients will be treated with Berberine, 50 mg p.o., tid
Sponsors
Fujian Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * ECOG performance status 0-2 * Adequate haematological function, coagulation, liver function and renal function * Pathological diagnosis of predominantly non-squamous, non-small-cell lung cancer (NSCLC) * TNM version 7 stage IV disease including M1a (malignant effusion) or M1b (distant metastasis), or locally advanced disease not amenable to curative treatment (including patients progressing after radiochemotherapy for stage III disease) * Measurable or evaluable disease (according to RECIST 1.1 criteria). * Centrally confirmed EGFR exon 19 deletion (del19) or exon 21 mutation (L858R)
Exclusion criteria
* Patients who have had in the past 5 years any previous or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ breast carcinoma. Patients with any known significant ophthalmologic anomaly of the ocular surface * Patients who received prior chemotherapy for metastatic disease * Patients who received previous treatment for lung cancer with drugs targeting EGFR or VEGF * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient | Time from the date of enrolment to discontinuation of treatment for any reason (including progression of disease, treatment toxicity, refusal and death) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response | through study completion,an average of three years | Best overall response (complete remission or partial remission) across all assessment time-points according to RECIST Criteria 1.1, during the period from enrolment to termination of trial treatment. |
| safety | Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient | Adverse events graded according to NCI CTCAE V4. |
Countries
China
Contacts
Primary ContactGen Lin, Dr.
Outcome results
None listed