Gefitinib and Berberine in the First-line Treatment of Lung Adenocarcinoma With EGFR Mutation

Fujian Cancer Hospital50 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Lung Adenocarcinoma EGFR Mutation

Interventions

gefitinibDRUG

Patients will be treated with gefitinib, 250 mg p.o., daily

BerberineDRUG

Patients will be treated with Berberine, 50 mg p.o., tid

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Fujian cancer hospital

Fuzhou, Fujian, China

Outcomes

Primary Outcomes

Progression free survival

Time from the date of enrolment to discontinuation of treatment for any reason (including progression of disease, treatment toxicity, refusal and death)

Time frame: Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient

Secondary Outcomes

Objective response

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.

Time frame: through study completion,an average of three years

safety

Adverse events graded according to NCI CTCAE V4.

Time frame: Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient

Central Contacts

Gen Lin, Dr.

CONTACT

00861-591-83660063 lingen197505@163.com

Data from ClinicalTrials.gov

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