An Open-label Phase II Trial of Gefitinib and Berberine in Patients With Advanced Non-small Cell Lung Cancer and Activating EGFR Mutations
试验速览
- 阶段
- 2 期
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Progression free survival
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Gefitinib and Berberine
Experimental: Gefitinib and Berberine Patients will be treated with Gefitinib and Berberine. Gefitinib: 250 mg p.o., daily. Berberine: 50 mg p.o., tid.
干预措施: gefitinib (Drug)
Gefitinib and Berberine
Experimental: Gefitinib and Berberine Patients will be treated with Gefitinib and Berberine. Gefitinib: 250 mg p.o., daily. Berberine: 50 mg p.o., tid.
干预措施: Berberine (Drug)
结局指标
主要结局
Progression free survival
时间窗: 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)
次要结局
- safety(Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient)
- Objective response(through study completion,an average of three years)