Clinical trial NCT03486496: Gefitinib and Berberine in the First-line Treatment of Lung Adenocarcinoma With EGFR Mutation
Official title: An Open-label Phase II Trial of Gefitinib and Berberine in Patients With Advanced Non-small Cell Lung Cancer and Activating EGFR Mutations
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Lung Adenocarcinoma
EGFR Mutation
Keywords: Lung Adenocarcinoma
EGFR mutation
Gefitinib
Berberine
Lead sponsor: Fujian Cancer Hospital
Sponsor class: OTHER_GOV
First posted: 2018-04-03
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival
timeFrame: Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient
Secondary outcomes:
measure: Objective response
timeFrame: through study completion,an average of three years
measure: safety
timeFrame: Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Fujian cancer hospital
state: Fujian
Study officials:
affiliation: Fujian Cancer Hospital
name: Cheng Huang, MD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fan XX, Leung EL, Xie Y, Liu ZQ, Zheng YF, Yao XJ, Lu LL, Wu JL, He JX, Yuan ZW, Fu J, Wei CL, Huang J, Xiao DK, Luo LX, Jiang ZB, Zhou YL, Kam RK, Liu L. Suppression of Lipogenesis via Reactive Oxygen Species-AMPK Signaling for Treating Malignant and Proliferative Diseases. Antioxid Redox Signal. 2018 Feb 10;28(5):339-357. doi: 10.1089/ars.2017.7090. Epub 2017 Aug 4.