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

Lung Adenocarcinoma Clinical Trial

— Geber  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03486496
• Other study ID #: CSWOF201801
• Status: Not yet recruiting
• Phase: Phase 2
• First received: March 24, 2018
• Last updated: March 31, 2018
• Start date: June 5, 2018
• Est. completion date: February 1, 2020

Study information

• Verified date: March 2018
• Source: Fujian Cancer Hospital
• Contact: Gen Lin, Dr.
• Phone: 00861-591-83660063
• Email: lingen197505[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: February 1, 2020
• Est. primary completion date: June 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• EGFR Mutation
• Lung Adenocarcinoma
• Lung Neoplasms

Intervention

Drug:
• gefitinib
Patients will be treated with gefitinib, 250 mg p.o., daily
• Berberine
Patients will be treated with Berberine, 50 mg p.o., tid

Locations

Country	Name	City	State
China	Fujian cancer hospital	Fuzhou	Fujian

Sponsors (1)

Lead Sponsor	Collaborator
Fujian Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (1)

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 Pro — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient
Secondary	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.	through study completion,an average of three years
Secondary	safety	Adverse events graded according to NCI CTCAE V4.	Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient