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

Fujian Provincial Cancer Hospital

Status and phase: Unknown; Phase 2

Conditions: EGFR Mutation; Lung Adenocarcinoma

Treatments: Drug: Berberine; Drug: gefitinib

Study type: Interventional

Funder types: Other

Identifiers

NCT03486496

CSWOF201801

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

50 participants in 1 patient group

Gefitinib and Berberine

Experimental group

Description:

Experimental: Gefitinib and Berberine Patients will be treated with Gefitinib and Berberine. Gefitinib: 250 mg p.o., daily. Berberine: 50 mg p.o., tid.

Treatment:

Drug: gefitinib

Drug: Berberine